breast cancer bone metastasis lytic or blastic

2010, 33 (3 Suppl): S1-7. Cancer. PubMed Breast cancer frequently metastasizes to the skeleton, interrupting the normal bone remodeling process and causing bone degradation. Google Scholar. In males, prostate and lung cancers make up 80% of carcinomas metastasising to bone. They activate latent molecules released from the matrix. Clarke BL, Khosla S: Physiology of bone loss. In people with breast and prostate cancer, the bone is often the first distant site of cancer spread. Clinical Characteristics, Prognostic Factors and Treatment Outcomes of Patients with Bone-Only Metastatic Breast Cancer. Disclaimer, National Library of Medicine Larkins TL, Nowell M, Singh S, Sanford GL: Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression. Khosla S: Minireview: the OPG/RANKL/RANK system. 2010, 29: 811-821. CAS 1993 Jun 1;90(11):5021-5 Feng X, McDonald JM: Disorders of bone remodeling. Adv Drug Deliv Rev. Osteo-blasts also produce osteoprotegerin (OPG), a decoy receptor to RANKL that curtails osteoclast activation. While breast cancer metastases can have blastic and lytic lesions, myeloma bone lesions are purely osteolytic due to increased osteoclast activity and suppressed osteoblast activity . Their multifunctionality demonstrates their importance. Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J: A multigenic program mediating breast cancer metastasis to bone. MMPs are involved in the bone remodeling process after osteoclasts are finished. Heterogeneity of tumor cells in the bone microenvironment: Mechanisms and therapeutic targets for bone metastasis of prostate or breast cancer. 2006, 12: 1431-1440. It should be noted that in addition to obvious members of the vicious cycle, other factors are produced during the process, including inflammatory cytokines, which significantly affect tumor cell survival, cell differentiation, and angiogenesis. Bone metastases are areas of cancer that develop when breast cancer cells travel to the bones. 2004, 21: 427-435. Breast cancer-derived factors facilitate osteolytic bone metastasis. 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. Cancer Treat Rev. Troen BR: Molecular mechanisms underlying osteoclast formation and activation. 2000 Mar;18(6):1378-91. doi: 10.1200/JCO.2000.18.6.1378. Stopeck A: Denosumab findings in metastatic breast cancer. Akech J, Wixted JJ, Bedard K, van der Deen M, Hussain S, Guise TA, van Wijnen AJ, Stein JL, Languino LR, Altieri DC, Pratap J, Keller E, Stein GS, Lian JB: Runx2 association with progression of prostate cancer in patients: mechanisms mediating bone osteolysis and osteoblastic metastatic lesions. J Cell Biochem. McHayleh W, Ellerman J, Roodman D: Hematologic malignancies and bone. According to this paradigm, the tumor cells produce a variety of growth factors, most notably parathyroid hormone-related protein (PTHrP) [18]. Once activated the large multinucleated osteoclasts attach to the bone surface creating a resorption lacuna, a sealed zone in which acid and proteolytic enzymes, such as cathepsin K, are released and degrade the bone matrix. As primary constituents in bone metabolism, calcium and vitamin D can not be overlooked as critical regulators of osteolysis in bone metastatic breast cancer. Article eCollection 2022. 2010, 70: 6537-6547. Before 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. These molecules cause osteoblasts not only to form new bone but also to release RANKL and other osteoclastic mediators. Below are the links to the authors original submitted files for images. This process is effected by osteoblasts and osteoclasts within a functional and anatomic unit known as the basic multicellular unit (BMU). It is a reservoir of numerous growth factors as well as calcium and phosphorous, which are released from the matrix during bone remodeling. Rucci N, Millimaggi D, Mari M, Del Fattore A, Bologna M, Teti A, Angelucci A, Dolo V: Receptor activator of NF-kappaB ligand enhances breast cancer-induced osteolytic lesions through upregulation of extracellular matrix metalloproteinase inducer/CD147. Mercer RR, Miyasaka C, Mastro AM: Metastatic breast cancer cells suppress osteoblast adhesion and differentiation. In reality the system is much more complex (Table 1). A large-scale 2017 study of the 10 most common cancers with bone metastasis found: Lung cancer had the lowest 1-year survival rate after bone metastasis (10 percent). In the process, growth factors stored in the matrix, such as transforming growth factor (TGF)-, vascular endothelial growth factor (VEGF), insulin-like growth factors (IGFs), bone morphogenic proteins and fibroblast-derived factors, as well as calcium, are released into the bone microenvironment. Their function is not clear except that their retraction is necessary for bone resorption to begin [10]. Induction of aberrant osteoclastogenesis is only part of the equation. 2005, 5 (Suppl): S46-53. To accomplish the process of metastasis to bone, breast cancer cells are required to intrinsically possess or acquire the capacities that are necessary for them to proliferate, invade, migrate, survive, and ultimately arrest in bone. Disclaimer, National Library of Medicine Bone metastasis can cause pain and broken bones. Osteomimetic factors driven by abnormal Runx2 activation in breast cancer cells may increase their survival in the bone microenvironment. 10.1097/COC.0b013e3181deb9e5. 10.1097/SPC.0b013e32832f4149. While COX-1 is constitutively expressed in most tissues, COX-2 expression appears to be limited to brain, kidney, bone, reproductive organs and some neoplasms. Bethesda, MD 20894, Web Policies Evidence from an intratibial bone metastasis model indicates that when highly aggressive metastatic MDA-MB-231 cells express dysfunctional Runx2 or small hair-pin RNA for Runx2, both osteoclastogenesis and osteolytic lesions decrease [40]. Provided by the Springer Nature SharedIt content-sharing initiative. Matrix degradation appears to be only one of the roles of MMPs. 2010, 3: 572-599. 10.3322/canjclin.57.1.43. Ooi LL, Zhou H, Kalak R, Zheng Y, Conigrave AD, Seibel MJ, Dunstan CR: Vitamin D deficiency promotes human breast cancer growth in a murine model of bone metastasis. Kozlow W, Guise TA: Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. 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. PubMed Guise TA: Parathyroid hormone-related protein and bone metastases. 10.1038/sj.emboj.7600729. Biochem Biophys Res Commun. Cholesterol Synthesis Is Important for Breast Cancer Cell Tumor Sphere Formation and Invasion. Osteoblasts also produce osteoprotegerin (OPG), a decoy receptor to RANKL. In the highly metastatic, COX-2-expressing breast cancer cell line Hs578T, treatment with the selective COX-2 inhibitor Ns-398 markedly decreased the production of MMP1, 2, 3, and 13 in a dose-dependent manner. 2005, 10: 169-180. In light of these findings, correction of calcium and vitamin D deficiencies should be considered as adjuvant therapies in slowing or preventing osteolysis in breast cancer patients. 2008, 34 (Suppl 1): S25-30. Thus, bone loss is due to both increased activation of osteoclasts and suppression of osteoblasts. Fragments of human fetal bone implanted in SCID mice allow one to examine human cancer with human bone [76]. 2022 Jul 20;14(14):3521. doi: 10.3390/cancers14143521. Breast cancer metastasis to the bone: mechanisms of bone loss, http://breast-cancer-research.com/series/metastasis_pathway. Miao W, Ti Y, Lu J, Zhao J, Xu B, Chen L, Bao N. Front Chem. 10.1056/NEJMe1010459. American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. For females, breast and lung are the most common primary sites ; nearly 80% of cancers that spread to the skeleton are from these locations. The blastic bone lesions are caused when the cancer cells release the fluids. It's the most advanced stage of breast cancer. Accessibility 10.1056/NEJMoa030847. Orr and colleagues [5] have determined MMPs sufficient to resorb bone in vitro and to contribute to the process in vivo. MeSH 2021 Dec 1;31:100407. doi: 10.1016/j.jbo.2021.100407. Cancer Treat Rev. Epidemiological studies have also correlated the increase in breast cancer rates with decreasing sunlight exposure. Breast cancer is often compared with prostate cancer, which metastasizes to the skeleton with a similar frequency. Cathepsin K is the major mediator of bone resorption, controlling the osteoclast portion of the vicious cycle. These molecules bind to hydroxyapatite of the bone matrix and are ingested by osteoclasts, which then undergo apoptosis. Nevertheless, they do not appear to function in the osteoclast resorption lacuna, probably due to the low pH in this compartment. Chemotherapy may bring about ovarian failure and premature menopause [1]. However, both bone degradation and deposition likely occur early in the metastatic process. Cancer Cell. IL-8, a proinflammatory CXC chemokine, is secreted by monocytes, endothelial cells and osteoblasts. 2005, 310: 270-281. -, Cancer Metastasis Rev. However, PTHrP does not directly stimulate osteoclast differentiation, but rather stimulates other cells to increase RANKL and decrease OPG production. Breast, prostate, and lung cancers represent the main sources of bone metastases, with prostate and lung cancers being most common in males and breast cancer being most common in females . 10.1007/s10585-007-9112-8. 10.1158/0008-5472.CAN-09-2758. PubMed Carlsten H: Immune responses and bone loss: the estrogen connection. This is a disease of clonal malignancy of terminally differentiated plasma cells that accumulate in the bone marrow. N Engl J Med. Edited by: Rosen CL. HHS Vulnerability Disclosure, Help Using this device, we have been able to grow osteoblasts into a mineralized tissue. Purpose: This is a study in adult patients with different types of cancer. 2009, 175: 1255-1269. 2010, 48: 483-495. Understanding the mechanisms of osteolysis should be the key to designing the cure. Metastastic human breast cancer cells (MDA-MB-231) added to this culture attach, penetrate the tissue and form single cell files characteristic of metastases seen in pathologic tissues. In males, prostate and lung cancers make up 80% of carcinomas metastasizing to bone. 2010, 126: 1749-1760. 8600 Rockville Pike American Society of Clinical Oncology Bisphosphonates Expert Panel. Treatment can be tailored for each patient and, often requires multiple therapeutic interventions. Morrissey C, Lai JS, Brown LG, Wang YC, Roudiffer MP, Coleman IM, Gulati R, Vakar-Lopez F, True LD, Corey E, Nelson PS, Vessella RL: The expression of osteoclastogenesis-associated factors and osteoblast response to osteolytic prostate cancer cells. official website and that any information you provide is encrypted VEGF also forms a complex with the extracellular matrix [31, 55]. J Biomol Tech. (A) The bone microenvironment under conditions of normal bone remodeling; (B) and in the presence of osteolytic bone metastases. Bisphosphonates binding to hydroxyapatite are ingested by osteoclasts and cause their apoptosis. It can activate osteoclasts independent of RANKL [21]. Current therapies consist of blocking osteoclast activity as a means of disrupting the vicious cycle. However, breast cancer cells are unable to progress in bone unless they destroy bone with the assistance of bone-resorbing osteoclasts. Pharmaceuticals. 10.1111/j.1749-6632.1974.tb14480.x. Clezardin P, Teti A: Bone metastasis: pathogenesis and therapeutic implications. 2016 Apr 1;99(Pt B):206-211. doi: 10.1016/j.addr.2015.11.017. Parathyroid hormone-related protein and bone metastases. The site is secure. What Are The Symptoms Of Bone Metastasis In Breast Cancer. 1984, 235: 561-564. J Natl Compr Canc Netw. In addition, production of inflammatory cytokines (that is, IL-6, TNF-, M-CSF, IL-1) is suppressed by estrogen [64]. Takahashi T, Uehara H, Bando Y, Izumi K: Soluble EP2 neutralizes prostaglandin E2-induced cell signaling and inhibits osteolytic tumor growth. Please enable it to take advantage of the complete set of features! 10.1038/sj.bjc.6602417. Google Scholar, Mundy GR: Bone Remodeling and its Disorders. Clinical evidence indicates that this drug can reduce the rate of bone loss, but is not curative. Bone Rep. 2022 Jun 12;17:101597. doi: 10.1016/j.bonr.2022.101597. Klein DC, Raisz LG: Prostaglandins: stimulation of bone resorption in tissue culture. Kingsley LA, Fournier PG, Chirgwin JM, Guise TA: Molecular biology of bone metastasis. Breast cancer bone metastases: pathogenesis and therapeutic targets. Home; Study Search; Study Details From Other Databases This release of fluids and substances soon turns on the osteoblasts, which leads to the formation of new bone. Shimo T, Okui T, Horie N, Yokozeki K, Takigawa M, Sasaki A. The main symptoms of breast cancer that has spread to bone are: 2000, 2: 737-744. Doctors use imaging tests, such as x-rays, to figure out the types of . Osteoblastic or blastic metastases cause an area of the bone to look denser or sclerotic. 10.1210/er.19.1.18. 2009, 3: 213-218. At least three essential molecules, TGF-, IGF, and VEGF, need to be activated by MMPs before they can function. Aldridge SE, Lennard TW, Williams JR, Birch MA: Vascular endothelial growth factor acts as an osteolytic factor in breast cancer metastases to bone. This feature accounts for the variable sensitivity and specificity of different imaging modalities. 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]. 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. Proteolytic cleavage of SPARC releases biologically active cleavage products that affect angiogenesis factors such as VEGF, platelet-derived growth factor (PDGF) and FGF-2. Clin Breast Cancer. Endocr Rev. Other molecules made by multiple myeloma cells, such as IL-3, IL-7 and soluble frizzle-related protein-2, also inhibit osteoblast differentiation [27]. 2010, 115: 140-149. Bisphosphonates such as zoledronic acid (Zoledronate) bind to hydroxyapatite of the bone matrix and are ingested by osteoclasts, which then undergo apoptosis. These molecules not only help support tumor cells, but also are osteoclastogenic. Recently, we have found that metastatic breast cancer cells have profound effects on osteoblasts in culture [22] and in animals [31, 32]. Chen, YC., Sosnoski, D.M. MMP1, 2, 3 process the binding factors and free IGF, allowing it to bind to its receptors found both on osteoblasts and osteoclasts. CAS Br J Cancer. EMBO J. Retrieval of the bone at specific times gives a snapshot of the status of metastases. RANKL and other pro-osteoclastogenic cytokines are increased with a concomitant reduction in OPG, resulting in more osteoclast formation and bone degradation. It is common to find increased PTHrP serum levels in breast cancer patients. Oncogene. Metastasis of breast cancer cells to bone consists of multiple sequential steps. Annu Rev Pathol. Mol Cancer Ther. Mundy GR, Sterling JL: Metastatic solid tumors to bone. Metastases leading to overall bone loss are classified as osteolytic. Article Coenegrachts L, Maes C, Torrekens S, Van Looveren R, Mazzone M, Guise TA, Bouillon R, Stassen JM, Carmeliet P, Carmeliet G: Anti-placental growth factor reduces bone metastasis by blocking tumor cell engraftment and osteoclast differentiation. 1970, 86: 1436-1440. It can activate both Smad-dependent and Smad-independent signal pathways to induce preosteolytic factors such as PTHrP [23]. There are two types of lesions: lytic lesions, which destroy bone material; and blastic lesions, which fill the bone with extra cells. Dysfunctional Runx2 results in the developmental arrest of osteoblasts and inhibition of osteogenesis. Bethesda, MD 20894, Web Policies Further, we describe future directions for bone metastasis management, focusing on novel bone-specific targeted therapies. 10.1016/j.rcl.2010.02.014. PubMed Thus, in the course of the osteolytic process, the osteoblasts are unable to fulfill their role as bone building cells. In the early 1970 s it was reported that prostaglandins could resorb fetal bone in culture [43], and that aspirin, a COX-1 inhibitor, and indomethacin, a COX-2 inhibitor, could prevent osteolysis in tissue culture [44].