Other articles in the series can be found online at http://breast-cancer-research.com/series/metastasis_pathway, extracellular matrix metalloproteinase inducer, secreted protein acidic and rich in cysteine: osteonectin/BM-40, Lipton A, Uzzo R, Amato RJ, Ellis GK, Hakimian B, Roodman GD, Smith MR: The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors. Teriparatide, in contrast to bisphosphonates and denosumab, acts on osteoblasts to stimulate bone formation. Drugs of the bisphosphonate family have been used for many years as the standard of care. Exp Gerontol. Below are the links to the authors original submitted files for images. All in all, PTHrP is an important mediator between breast cancer cells and cells of the bone microenvironment and, as such, is a major contributor to the bone degradation process. Springer Nature. Another drug, teriparatide (Forteo), the amino-terminal 34 amino acids of parathyroid hormone, has been used for many years to treat osteoporosis. Increased production of EMMPRIN in turn leads to increases in VEGF and MMPs. Cancer of unknown primary origin Mundy GR, Sterling JL: Metastatic solid tumors to bone. 2005, 24: 2543-2555. Osteolytic lesions, also called osteoclastic or lytic lesions, are areas of damaged bone that most often occur in people with certain cancers, such as multiple myeloma and breast cancer. Metastatic breast cancer cells or their conditioned media increase osteoblast apoptosis, and suppress osteoblast differentiation and expression of proteins required for new bone matrix formation. In fact, a new drug, denosumab (Prolia), a fully human monoclonal antibody to RANKL, has been approved by the US Food and Drug Administration (FDA) for the treatment of postmenopausal women with high risk of osteoporotic fractures, and is under priority review for patients with bone metastases. PTHrP is expressed in the primary tumors of about 50% of patients and in more than 90% of breast cancer bone metastasis samples [18]. In the final stages of metastatic osteolytic breast cancer disease, the cancer cells, fueled by growth factors released from the degraded matrix, expand unchecked. Cancer Res. Furthermore, Pozzi and colleagues [30] have recently reported that high doses of zoledronic acid, the current standard therapeutic for most osteolytic diseases, may also negatively affect osteoblast differentiation. Most patients were diagnosed with the common cancers that metastasize to bone, that is, lung (13), kidney (7), prostrate (7), breast (3). Breast cancer is often compared with prostate cancer, which metastasizes to the skeleton with a similar frequency. Several of these RANKL inducers merit further discussion with respect to metastatic breast cancer-induced osteolysis. The dynamics of this system are interrupted when metastatic breast cancer cells are introduced, adding another layer of active molecules to the bone environment. 10.1007/s10585-007-9112-8. N Engl J Med. The roentgenogram indicates the net effect of these two processes. 2008, 473: 98-105. Retrieval of the bone at specific times gives a snapshot of the status of metastases. AMM, the senior investigator and corresponding author, has worked in the area of breast cancer metastasis to bone for over 12 years. 2003, 300: 957-964. While the case for the importance of MMPs as metastasis regulators is strong, they themselves are regulated by tissue inhibitors of metalloproteinase (TIMPs). Standal T, Borset M, Sundan A: Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Chen, YC., Sosnoski, D.M. PubMed Central Bone. Osteo-blasts also produce osteoprotegerin (OPG), a decoy receptor to RANKL that curtails osteoclast activation.
1986; (203): 282-8.
2010, 33 (3 Suppl): S1-7. Cancer Res. Part of this uncertainty is because we do not fully understand all of the cell, cytokine and growth factor interactions that occur in the bone microenvironment. Common treatments for bone metastasis include medications, radiation therapy and surgery. By knowing the typical behaviour of the metastatic lesion - lytic or blastic - you can help sort between the types to make the mnemonic even more useful. Google Scholar, Mundy GR: Bone Remodeling and its Disorders. Runx2 downregulates proliferation and induces p21, RANKL, MMP2, MMP9, MMP13, VEGF, OPN, bone sialoprotein and PTHrP protein expression to promote osteoblast differentiation, bone development and turnover [39]. In addition, pre-clinical trials with agents that target cathepsin K, certain matrix metalloproteinases (MMPs), and transforming growth factor (TGF)- are underway. Thorax. Clarke BL, Khosla S: Physiology of bone loss. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Cells of the monocyte-macrophage lineage are stimulated to form osteoclast progenitor cells. Bone provides support and protects vital organs but also is a metabolically active tissue. CAS
10.1016/S8756-3282(03)00086-3. Thus, bone loss is due to both increased activation of osteoclasts and suppression of osteoblasts. Results from the Thus, in the course of the osteolytic process, the osteoblasts are unable to fulfill their role as bone building cells. As primary constituents in bone metabolism, calcium and vitamin D can not be overlooked as critical regulators of osteolysis in bone metastatic breast cancer. Andrea M Mastro. 10.1038/onc.2009.389. 2010. RANKL clearly holds the key to the osteolytic process. This information is not easily obtained with in vitro studies. 2010, 29: 811-821. Brief desc of tx There is virtually no role of curative surgery. Treatment options for MBD often depend on where the bone metastases have developed. Correspondence to H Singh and JA Neutze (eds. Clin Orthop Relat Res. Br J Cancer. Aldridge SE, Lennard TW, Williams JR, Birch MA: Vascular endothelial growth factor acts as an osteolytic factor in breast cancer metastases to bone. The presence of skeletal metastases in patients suffering from cancer leads to a variety of clinical complications. 10.1158/0008-5472.CAN-08-1078. Since the discovery of RANKL and its role in bone remodeling, the field of bone metastasis has moved rapidly.
J Biomol Tech. (a) CT of the T6 vertebra in a patient with breast cancer demonstrates a mixed lytic/blastic metastasis in the anterior aspect of the vertebral body. However, cathepsin K is also produced by other cells in the bone microenvironment, such as macrophages and bone marrow stromal cells. Basic knowledge of a simple mnemonic about the main types of bone metastases can be a handy tip in the medical routine:with a good history taking from the patient,clinical findings and sharp eyes on the images it is possible to nail a nice and elegant diagnostic hypothesis allowing a more specific investigation. Neutralization of TGF- in conditioned medium from human metastatic MDA-MB-231 breast cancer cells permitted the differentiation of osteoblasts in culture, suggesting that TGF- negatively affects osteoblasts while promoting growth of the metastatic cells [33]. ( Table 1 ) effect on osteoblasts to stimulate bone formation predominates, spatial. ; Arie Perry, Daniel J. 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Clin. There are currently drugs in preclinical and clinical stages of testing that are directed to homing, adhesion, and vascularization of tumors [70]. Cancer Res. Bendre M, Montague DC, Peery T, Akel NS, Gaddy D, Suva LJ: Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Klein DC, Raisz LG: Prostaglandins: stimulation of bone resorption in tissue culture. Chronic inflammation has long been considered a risk factor in cancer initiation [68]. Breast cancer frequently metastasizes to the skeleton, interrupting the normal bone remodeling process and causing bone degradation.
2010, 115: 140-149. Bone. - American Cancer Society - http://www.cancer.org/treatment/understandingyourdiagnosis/bonemetastasis/bone-metastasis-key-statistics1, 10. There are conflicting reports regarding their effect on osteoblasts. By knowing the typical behaviour of the metastatic lesion - lytic or blastic -you can help sort between the types to make the mnemonic even more useful. Bone. They activate latent molecules released from the matrix. 10.1182/blood-2009-08-237628. 10.1158/0008-5472.CAN-10-2179. 7. At higher doses they may in fact prevent osteoblast differentiation [30]. Once osteoblasts finish bone deposition, they undergo apoptosis, remain in the matrix as osteocytes or revert to thin bone-lining cells. The vertebral vein system. J Cell Biochem. In the next step, preosteoblasts are recruited from the mesenchymal stem cell population and differentiate into osteoblasts. 1999, 59: 1987-1993. Grey A: Teriparatide for bone loss in the jaw. After your cancer is gone, it is the job of the osteoblasts to rebuild the bone. Proff P, Romer P: The molecular mechanism behind bone remodelling: a review. Osteoblasts and bone stromal cells can respond to a variety of substances that upregulate RANKL. Estrogen also increases osteoblast pro-collagen synthesis and decreases osteoblast apoptosis [63]. The bone microenvironment. The clinical outcomes of bone pain, pathologic fractures, nerve compression syndrome, and metabolic disturbances leading to hypercalcemia and acid/base imbalance severely reduce the quality of life [3]. What initiates remodeling in the non-tumor-containing bone? Ganapathy V, Ge R, Grazioli A, Xie W, Banach-Petrosky W, Kang Y, Lonning S, McPherson J, Yingling JM, Biswas S, Mundy GR, Reiss M: Targeting the transforming growth factor-beta pathway inhibits human basal-like breast cancer metastasis. Both RANKL and VEGF can induce osteoclast formation [48], and MMPs play a role in bone matrix degradation. Ohshiba T, Miyaura C, Ito A: Role of prostaglandin E produced by osteoblasts in osteolysis due to bone metastasis. 10.1097/SPC.0b013e32832f4149. CA Cancer J Clin. Stopeck A: Denosumab findings in metastatic breast cancer. Corisdeo S, Gyda M, Zaidi M, Moonga BS, Troen BR: New insights into the regulation of cathepsin K gene expression by osteoprotegerin ligand. Ganapathy and colleagues [24] found that TGF- antagonists are able to reduce bone metastasis and the number and activity of differentiated osteoclasts [24]. Minimally invasive percutaneous ablative treatment techniques, including radiofrequency ablation, microwave ablation, and cryoablation, are examined. Cancer can cause bone to break down and leak calcium. Mundy GR: Mechanisms of bone metastasis. After your cancer is gone, it is the job of the osteoblasts to rebuild the bone. To date, osteoclasts have been the primary target of drug therapies. Arch Biochem Biophys.
The resorption phase of the process begins with recruitment of pre-osteoclasts that differentiate into activated osteoclasts under the direction of osteoblasts (Figure 1A). At the time the article was last revised Daniel J Bell had Breast cancer cells also cause inhibition of osteoblast differentiation and adhesion, downregulation of collagen synthesis and increased osteoblast apoptosis. J Natl Compr Canc Netw. As pointed out by Lynch, the spatial and temporal expression of these molecules is of utmost importance. DMS is a senior research technician with many years experience in the bone field. 1984, 235: 561-564. Metastatic cancer cells tend to colonize the heavily vascularized areas of the skeleton, such as the red marrow of the long bones, sternum, pelvis, ribs and vertebrae, where they disrupt not only bone physiology but also hematopoiesis and the immune system [3]. WebBone metastases are areas of cancer that develop when breast cancer cells travel to the bones. In normal bone remodeling, osteoclasts secrete PDGF, which acts as a chemoattractant to recruit pre-osteoblasts to the site of bone repair [58]. Multiple myeloma is a malignant tumor of plasma cells that causes lytic bone damage. Pratap J, Wixted JJ, Gaur T, Zaidi SK, Dobson J, Gokul KD, Hussain S, van Wijnen AJ, Stein JL, Stein GS, Lian JB: Runx2 transcriptional activation of Indian Hedgehog and a downstream bone metastatic pathway in breast cancer cells. Bisphosphonates such as zoledronic acid (Zoledronate) bind to hydroxyapatite of the bone matrix and are ingested by osteoclasts, which then undergo apoptosis. 2005, 92: 1531-1537. Osteoclasts derive from hematopoietic stem cells. In addition, PDGF has been shown to inhibit osteoblast differentiation [60], making it an important factor in bone remodeling and the osteolytic bone metastasis. Article Mol Cancer Ther. 2010;65 (3): 241-5. Google Scholar. Hadjidakis DJ, Androulakis II: Bone remodeling. More than 2 out of 3 breast and prostate cancers that spread to other parts of the body spread to the bones. Cancer Cell. WebBone metastases to the finger. Coleman R, Gnant M: New results from the use of bisphosphonates in cancer patients. Teriparatide is a recombinant peptide of parathyroid hormone that stimulates osteoblast activity and bone formation. The use of blocking antibodies to placental growth factor in two xenograft mouse/human models greatly decreased the numbers and size of osteolytic lesions [61]. While drugs that inhibit osteoclast differentiation or activity are vital to treating osteolysis, therapies designed to restore osteoblast number and function will be required to fully resolve osteolytic lesions. Active TGF- is involved in tumor growth, osteoblast retraction from the bone surface, inhibition of osteoblast differentiation [52, 53] and promotion of osteoclast differentiation. 2008, 68: 7795-7802. The tumors that develop, sometimes called lesions, can: Make the bones weaker Imagingby skeletal scintigraphy, plain radiography, computed tomography, or magnetic resonance imagingis an essential part, and positron emission tomography or single-photon emission computed tomography have a potential of evaluating bone Where bone destruction predominates, it appears lytic. PTH/PTHrP, TNF-, prostaglandins (PGE2), IL-1, IL-11, FGF-2, and IGF-1 have been reported to increase RANKL production. They also are regulators of other molecules important in the vicious cycle. Webthyroid carcinoma - solitary metastasis, prostate adenocarcinoma - blastic metastasis, melanoma - lytic metastasis, osteosarcoma - metastasis in children, breast cancer - most common primary source of metastasis in adult females, Bone Metastases Share by Noordacom Edit Content Embed More Leaderboard Theme Options Switch template Clin Cancer Res. In this context, RANKL increases in the presence of inflammatory agents from infectious organisms, such as lipopolysaccharide, CpGpDNA and viral double-stranded DNA [41]. 2010. Mercer RR, Miyasaka C, Mastro AM: Metastatic breast cancer cells suppress osteoblast adhesion and differentiation. Curr Opin Support Palliat Care. 1998, 19: 18-54. In a series of in vitro, ex vivo and in vivo experiments, Ohshiba and colleagues [45] demonstrated that direct cell-cell contact between breast cancer cells and osteoblasts caused an increase in COX-2 expression in the osteoblasts due to activation of the NFB/mitogen-activated protein (MAP) kinase pathway. WebLytic lesions are essentially the hollowed-out holes where your cancer formerly existed. PubMed 2010, 70: 8329-8338. 10.2741/S110. Feng X, McDonald JM: Disorders of bone remodeling. Of the bisphosphonates, zoledronic acid is the most potent. & Mastro, A.M. Clin Oral Investig. Of course, the best cure for bone metastasis is prevention. Hung JJ, Jeng WJ, Hsu WH et-al. Guise TA: Parathyroid hormone-related protein and bone metastases. There is also evidence that molecules in conditioned medium from PC-3 cells alone [34], or from both PC-3 cells and MC3T3-E1 osteoblasts [35], promote osteoclastogenesis. The entry of breast cancer cells into the bone micro-environment synergistically increases the complexity of cell-cell interactions. 2008, 314: 173-183. Here we discuss some of the proposed mechanisms that contribute to metastatic breast cancer-induced bone loss. WebLung cancer metastases normally appear purely lytic, with poor margination, no matrix and cortical destruction. Minimally invasive percutaneous ablative treatment techniques, including radiofrequency ablation, microwave ablation, and cryoablation, are examined. Yang Y, Ren Y, Ramani VC, Nan L, Suva LJ, Sanderson RD: Heparanase enhances local and systemic osteolysis in multiple myeloma by upregulating the expression and secretion of RANKL. These types of tumors are called osteoblastic, or simply blastic. 10.1038/sj.bjc.6602417. According to this paradigm, the tumor cells produce a variety of growth factors, most notably parathyroid hormone-related protein (PTHrP) [18]. Zheng Y, Zhou H, Modzelewski JR, Kalak R, Blair JM, Seibel MJ, Dunstan CR: Accelerated bone resorption, due to dietary calcium deficiency, promotes breast cancer tumor growth in bone. Immunol Rev. The cyclooxygenase enzymes COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandins and thromboxanes. IGF, insulin-like growth factor; MCP-1, monocyte chemotactic protein-1; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor. It is now generally accepted that the bone microenvironment is critical to the colonization and growth or dormancy of metastases. Res. Cancer cells also can elicit an increase in osteoblast production of several other osteoclastogenic cytokines, such as monocyte chemotactic protein-1 (MCP-1) and IL-6, IL-8 and TNF [22]. Induction of aberrant osteoclastogenesis is only part of the equation. Because of its significant role, TGF- has been a tempting therapeutic target. Privacy Google Scholar. 2010, 2: 907-915. Despite the role of the osteoclasts in this process, the outcome is due in large part to the impact of cancer cells directly and indirectly on osteoblasts. Article Endocr Relat Cancer. Newer imaging modalities, such as positron emission tomography (PET)/CT, improve detection of both lytic and blastic metastases. 2010, 70: 6537-6547. Osteoblasts derive from mesenchymal stem cells in the marrow under control of Runx2, a key osteoblastic transcription factor. 2010, 363: 2458-2459. Just as osteoblasts are a critical partner in normal bone remodeling, they are vital to the metastatic osteolytic process. However, once bone metastasis has occurred, the aim has been to break the osteolytic cycle by targeting osteoclasts. Mechanisms of lytic and blastic metastatic disease of bone In the majority of skeletal metastases, new bone develops simultaneously with bone destruction. The roentgenogram indicates the net effect of these two processes. Where the bone formation predominates, the lesion appears sclerotic. WebIn the majority of skeletal metastases, new bone develops simultaneously with bone destruction. In the bone, OPN is involved in the differentiation and activity of osteoclasts, and inhibition of mineral deposition in the osteoid [37]. 2010. Article J Bone Miner Res. PDGF can function as a mitogen for cells of mesenchymal origin and possesses chemoattractant properties, making it an important factor in cell proliferation and migration. Edwards J. Src kinase inhibitors: an emerging therapeutic treatment option for prostate cancer. However, there is no guarantee that inhibition of osteolytic lesions would prevent the growth of cancer cells in the bone or their spread to other organs. Raica M, Anca M: Platelet-derived growth factor (PDGF)/PDGF receptors (PDGFR) axis as target for antitumor and antiangiogenic therapy. Metastasis describes the spread of cancer from where it started to another part of the body. This happens when cancer cells break from the primary tumor and enter the lymph system or bloodstream. From there, they can travel throughout the body and form new tumors. Metastatic breast cancer in bones is not the same as bone cancer. Akech and colleagues [34] recently reported that Runx2 (Runt-related transcription factor 2) is produced by the highly metastatic prostate cancer cell PC-3, and positively correlates to the severity of osteolytic disease. Clin Pharmacol Ther. 2005, 310: 270-281. 10.1111/j.0105-2896.2005.00326.x. J Dent Res.
2000, 2: 737-744. Surprisingly, this treatment did not affect angiogenesis in the bone. The results of an in vivo study showed that OPN-deficient mice showed significantly reduced bone metastasis [38]. Where do the MMPs come from? 2009, 15: 5829-5839. PubMed Understanding the mechanisms of osteolysis should be the key to designing the cure. Osteomimetic factors driven by abnormal Runx2 activation in breast cancer cells may increase their survival in the bone microenvironment. 2005, 208: 194-206. Rev Endocr Metab Disord. Cancer cells, osteoblasts, osteoclasts and endothelial cells produce MMPs. PDGF is a dimeric protein consisting of two of four possible subunits. When treated with neutralizing antibody to PDGF, the osteoblasts assumed normal morphology. The ratio of RANKL to OPG determines the extent of the osteoclast activity and bone degradation. 10.1097/00003086-200004000-00013. Further stimulation results in large multinuclear cells capable of bone resorption. Exp Cell Res. IL-11, normally produced by bone marrow stromal cells and osteoblasts, is an important regulator of hematopoiesis and a potent promoter of osteoclast formation. Recently, Roy and colleagues [69] investigated this association in a mouse model of autoimmune arthritis and found that arthritic mice had an increase in both lung and bone metastasis compared to the non-arthritic mice. It is common to find increased PTHrP serum levels in breast cancer patients. 2006, 23: 345-356. 2008, Washington, DC: American Society for Bone and Mineral Research, 374-378. full_text. Cancer. Blastic lesions are caused by new bone being made without old bone breaking Endocr Rev. 2010, 70: 1835-1844. 10.1196/annals.1365.035. PubMed Central Practical Surgical Neuropathology: A Diagnostic Approach; Arie Perry, Daniel J. Brat; Elsevier Health Sciences, 2010. 10.1007/s10911-005-5399-8. Prognostic factors of postrecurrence survival in completely resected stage I non-small cell lung cancer with distant metastasis. By using this website, you agree to our Another growth factor sequestered in the matrix is IGF. Zambonin Zallone A, Teti A, Primavera MV: Resorption of vital or devitalized bone by isolated osteoclasts in vitro.
Unable to process the form. MMP-9 is important in the cascade leading to activation of VEGFA. Cancer Treat Rev. 2008, 3: e3537-10.1371/journal.pone.0003537. Clin Breast Cancer. Annu Rev Pathol. prostate = Unfortunately, some of the therapies used for breast cancer patients may exacerbate the problem. Most patients were diagnosed with the common cancers that metastasize to bone, that is, lung (13), kidney (7), prostrate (7), breast (3). This approach will allow testing of components and drugs in a model less complex than an animal but more relevant than standard tissue culture. Google Scholar. Denosumab (Prolia), the latest drug to enter the field, is a monoclonal antibody to RANKL. Along with colleagues and students she has focused particularly on the fate of osteoblasts in the metastatic bone environment. Biochem Biophys Res Commun. In reality the system is much more complex (Table 1). Lynch CC: Matrix metalloproteinases as master regulators of the vicious cycle of bone metastasis. Current therapies consist of blocking osteoclast activity as a means of disrupting the vicious cycle. WebThe detection rate of bone metastases by BS in patients with early-stage breast cancer is very low (0.82% and 2.55% in patients with stages I and II, respectively), increasing to 16.75% in patients with stage III disease and 40.52% in pa-tients with stage IV disease. Those leading to excess bone deposition are considered osteoblastic. Front Biosci (Schol Ed). Cortical bone provides strength and protection while trabecular bone is the most metabolically active. There are two types of lesions: lytic lesions, which destroy bone material; and blastic lesions, which fill the Osteolytic lesions are the end result of osteoclast activity; however, osteoclast differentiation and activation are mediated by osteoblast production of RANKL (receptor activator for NFB ligand) and several osteoclastogenic cytokines. While ductal carcinoma in situ detected early is 98% curable, bone metastases are basically incurable [2]. PTHrP, one of many proteins controlled by Runx2, is a major effector in breast cancer bone metastasis progression and bone loss. 2009, 3: 213-218. However, both drugs are associated with low incidence of osteonecrosis of the jaw [75]. Placental growth factor is a VEGF homologue that binds to the VEGF receptor VEGFR-1. Vikesa J, Moller AK, Kaczkowski B, Borup R, Winther O, Henao R, et al. 2004, 26: 179-184. Current treatments can improve bone density, decrease skeletal related events and ease bone pain, yet existing bone lesions do not heal. 10.1016/j.ctrv.2010.04.003. 7. N Engl J Med. The PGE2-mediated production of RANKL induces osteoclastogenesis via RANK. Kingsley LA, Fournier PG, Chirgwin JM, Guise TA: Molecular biology of bone metastasis. However, because TGF- plays a more global role in cell proliferation and differentiation, its utility as a therapeutic may be limited. IGF binding initiates production of M-CSF and RANKL by osteoblasts and c-fms and RANK by osteoclasts [54]. Webblastic (bone formation), or mixed lesions (Fig 2). The skeleton is constantly undergoing remodeling. Dysfunctional Runx2 results in the developmental arrest of osteoblasts and inhibition of osteogenesis. Prostate. Breast Cancer Res 12, 215 (2010). There is evidence that bisphosphonates also contribute to tumor cell death, especially in combination with chemotherapy [72]. Bone is the most common site to which breast cancer metastasizes. It can activate osteoclasts independent of RANKL [21]. volume12, Articlenumber:215 (2010) Cancer Res. They are created when the cancer cells stimulate normal cells called osteoclasts to break down bone tissue in a process called resorption. It binds to two class III tyrosine kinase receptors, PDGFR and PDGFR, leading to activation of several signaling molecules. Edited by: Rosen CL. Provided by the Springer Nature SharedIt content-sharing initiative. Exp Oncol. Matrix degradation appears to be only one of the roles of MMPs. It is interesting that cancer cells often remain dormant in bone for many years before they begin to grow. Once osteoclasts are activated, they degrade bone matrix through several proteolytic enzymes, including MMPs and cathepsin K. Although cathepsin K is the major bone resorbing protease, MMPs, which are secreted by many cells, may be the 'master regulator' of the entire mechanism. 10.1006/bbrc.2001.5127. 4. Article Newer imaging modalities, such as positron emission tomography (PET)/CT, improve detection of both lytic and blastic metastases. 2003, 3: 537-549. Lerner UH: Bone remodeling in post-menopausal osteoporosis. 10.1002/(SICI)1097-0142(19971015)80:8+<1572::AID-CNCR7>3.0.CO;2-M. Karaplis AC, Goltzman D: PTH and PTHrP effects on the skeleton. In doing so, cancer cells are equipped to home, adhere, survive and proliferate in the bone microenvironment. 10.1158/0008-5472.CAN-08-4437. 2006, 12: 1431-1440. Oftentimes, small holes result from osteolysis. The MMPs are considered to be important in the bone metastatic process. Google Scholar. Endocrinology. COX-2 inhibition also partially attenuated the ability of two breast cancer cell lines to degrade and invade extracellular matrix components such as laminin and collagen [47]. Thus, Runx2 plays a significant role in the vicious cycle via TGF--induced IHH-PTHrP pathways in breast cancer cells, resulting in increased osteoclastogenesis and osteolysis. It is required to drive mesenchymal cells to become osteoblasts.
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breast cancer bone metastasis lytic or blastic