Most Common Site For Breast Cancer Metastasis – Metastatic breast cancer, also called metastases, advanced breast cancer, secondary tumors, secondary or stage IV breast cancer, is the stage of breast cancer in which breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer;
Metastases can occur years after the primary breast cancer, although sometimes they are diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer is diagnosed.
- 1 Most Common Site For Breast Cancer Metastasis
- 2 Bone Metastasis Of Breast Cancer
Most Common Site For Breast Cancer Metastasis
Metastatic breast cancer cells often differ from previous primary breast cancers in properties such as receptor status. These cells often develop resistance to several previous lines of treatment and have acquired special properties that allow metastasis to distant sites. Metastatic breast cancer is treatable, sometimes for years, but it is not curable.
How Does Breast Cancer Start & Spread?
Breast cancer can metastasize anywhere in the body but most commonly metastasizes to the bones, lungs, regional lymph nodes, liver and brain, with the most common site being bone.
Treatment of metastatic breast cancer depends on the location of the metastatic tumor and includes surgery, radiation, chemotherapy, biologicals, and hormonal therapy.
Typical vironmtal barriers in metastatic evt include physical components (basemt membrane), chemical (reactive oxygen species or ROS, hypoxia and low pH) and biological (immune surveillance, inhibitory cytokines and regulatory extracellular matrix (ECM) peptides).
Organ-specific anatomical considerations also affect metastasis; these include the blood flow pattern of the primary tumor and the ability of cancer cells to home to certain tissues. Targeting by cancer cells of specific organs may be regulated by chemo-attractant factors and adhesion molecules produced by the target organ, together with cell surface receptors expressed by tumor cells.
The Lingering Mysteries Of Metastatic Recurrence In Breast Cancer
Many breast cancer therapies (like targeted antibodies) fail to cross the blood-brain barrier, allowing tumors to recur in the central nervous system.
Pottial tumor cells for metastasis depds in its microvironmt, or “niche” interaction with local factors promoting tumor-cell growth, survival, angiogenesis, invasion and metastasis.
Cell-matrix and cell-ECM adhesion, motility, and local proteolysis are mediated primarily by matrix metalloproteases (MMPs). Degradation of the extracellular matrix initiates the process of metastasis. Cells develop structures called invadopodia, which are highly concentrated in several proteases and have a highly dynamic actin cytoskeleton.
Most of these processes require a delicate balance between the functions of matrix metalloproteases (MMPs) or metalloprotease-disintegrins (ADAMs) and natural tissue inhibitors of metalloproteases (TIMPs). Regulated proteolysis is an important mechanism for maintaining homeostasis. There is increased expression of the protease system in cancer cells, to complement the tools needed to break down the extracellular matrix and release growth factors or transmembrane receptors. MMP-2 was upregulated in bone, and increased levels of MMP-1 and MMP-19 were observed in the brain. It also, upregulates signaling pathways necessary to increase cell adhesion, cell motility, cell migration, invasion, cancer cell proliferation and survival.
Management Of Bone Metastases In Advanced Breast Cancer
ECM-tumor cell interactions play a critical role in each evts of the metastatic cascade. The interaction of breast cancer cells with integrins, fibronectin, laminin, collagen, hyaluronan and proteoglycans can contribute to the metastatic process. Some of these proteins are discussed here in relation to breast cancer metastasis.
Fibronectin is an extracellular glycoprotein that can bind integrins and other ECM components like collagen, fibrin and heparan sulfate proteoglycan (HSPG). Several different integrins bind to fibronectin. Fibronectin-integrin interactions are important in tumor cell migration, invasion, metastasis and cell proliferation by signaling through integrins. Integration-mediated adhesion of tumor cells to ECM proteins can trigger signal transduction and lead to upregulation of ge expression, increased tyrosine phosphorylation of focal adhesion kinase, and activation and nuclear translocation of mitog-activated protein (MAP) kinase.
Heparanase cleaves heparin sulfate chains from HSPGs, which have extensive networks with several proteins on the cell surface and ECM. The basic HSPG structure consists of a protein core to which several linear heparin sulfate (HS) chains are linked by covalent O; it acts as an assembly of different ECM proteins, including fibronectin, laminin, interstitial collagens, heparin-binding growth factors, chemokines and lipoproteins. HSPGs are important components of blood vessels.
For HS stabilizes fibroblast growth factors (FGFs) and vascular dothelial growth factors (VEGFs) and prevts from inactivation. The HS chain functions as a low-affinity co-receptor that promotes the dimerization of FGFs, helps in the sequestration of growth factors (GFs) and causes the activation of the receptor tyrosine kinase ev signal at low circulating concentrations of growth factors. Heparanase expressed by cancer cells participates in angiogenesis and neovascularization by degrading the BM dothelial polysaccharide scaffold, thereby releasing angiogenic growth factors from the ECM.
Bone Metastasis Of Breast Cancer
The ECM protein tascin C (TNC) is up-regulated in metastatic breast cancer. TNC is an adhesion-modulating extracellular matrix glycoprotein. It is highly expressed in the tumor stroma and stimulates the proliferation of tumor cells. It is thought that TNC stimulates invasion through the regulation of MMP-1 expression through the activation of the MAPK pathway. MMP-1 (interstitial collagenase) cleaves collagen types I, II, III, VII and X. Therefore, the overexpression of tascin C can alter the collagen in the ECM and cause the migration of tumor cells in the cartilaginous tissue.
Doglin is a cell surface disulfide-linked homodimeric glycoprotein that binds integrins and other RGD ligands and is a receptor for TGF-beta. Brain metastatic breast tumor cells secrete large amounts of doglin. doglin-overexpressing cells develop numerous invadopodia; doglin is localized to these structures. doglin expression in tumor cells contributes to metastasis by upregulating MMP-1 and MMP-19. MMP-19 cleaves basal lamina components such as collagen type IV, laminin 5, nidog (tactin) and other ECM proteins such as tascin, aggrecan and fibronectin. Therefore, overexpression of doglin alters the cell’s proteolytic balance to greater matrix degradation and enhances the invasive nature of breast cancer.
Integrin αvβ3 (cell surface adhesion molecule) is important for tumor attachment, cell-to-cell communication between breast tumor cells and vironmt in bone, osteoclast bone resorption and angiogenesis. Intergrin-mediated adhesion between cancer cells and osteoclasts in bone metastases induces phosphorylation of extracellular signal-regulated kinase (ERK1/2) in osteoclasts, which in turn leads to osteoclast differentiation and survival.
Metastatic breast cancer cells release lysophosphatidic acid (LPA) which binds to receptors on tumor cells, causing cell proliferation and releasing cytokines (IL-6 and IL-8, pott’s bone resorptive agts) and stimulating bone resorption. After breast cancer cells leave the primary tumor, these cells interact with bone microvirons and release osteolytic factors that can form osteoclasts and bone resorption. In addition to breast tumor cells, remaining stromal cells also contribute to tumor survival. Growth factors such as epidermal growth factor (EGF), fibroblast growth factor (FGF) and transforming growth factor beta (TGF-β) are implicated in the development and progression of metastatic breast cancer.
Mechanisms Of Drug Resistance In Breast Cancer Liver Metastases: Dilemmas And Opportunities: Molecular Therapy
MMP-2 is the main metalloprotease secreted by breast cancer cells or induced in the adjacent bone stroma; it plays an important role in the degradation of the extracellular matrix that is important for metastasis. Tumor cells use MMP-2 secreted by bone marrow fibroblasts (BMF). MMP-2 is kept in an inactive conformation associated with the cell surface (or extracellular matrix) of BMF.
Inactivated MMP-2 on the surface of BMF is displaced by breast cancer cells. Cancer cells can use proteinases to facilitate tissue invasion, which requires the degradation of connective tissue associated with the vascular basement membrane and interstitial connective tissue. MMP-2 is unlike other MMPs because its activity is modulated by a metalloprotease called tissue inhibitor of metalloproteases (TIMP) and membrane type 1 MMP (Korhmann et at. 2009)
The brain is a unique organ for metastasis, as breast tumor cells must cross the blood-brain barrier (BBB) to form micrometastases.
CD44 (cell surface transmembrane glycoprotein) is a receptor for hyaluronic acid, which is involved in cell adhesion by binding to certain extracellular matrix components. The mechanism proposed for the function of CD44 is to regulate the adhesion of cancer cells circulating in the brain to the dothelium at secondary sites with the help of hyaluronate matrix ligands or by cytoplasmic attachment to the actin-associated protein of merlin/ezrin. /radixin/moesin family.
Common Symptoms Of Metastatic Breast Cancer
Cell surface sialylation has been implicated in cell-to-cell interactions, and overexpression of brain sialyltransferase in breast cancer cells is a mechanism that highlights the role of cell surface glycosylation in organ-specific metastatic interactions. Breast cancer metastasis to the brain involves extravasation of mediators through non-festated capillaries, completed by specific hancers BBB-crossing and colonization of the brain.
The “seed and soil” hypothesis states that certain organs harbor metastases from one type of cancer by stimulating their growth better than other types of cancer. This interaction is dynamic and reciprocal, because cancer cells change vironmt they counter. Tumor embolus = seed and Target organ = soil.
In the detection of bone metastases, skeletal scintigraphy (bone scan) is very sensitive and is recommended as the first imaging study in asymptomatic individuals with suspected breast cancer metastases.
X-ray radiography is recommended in the presence of abnormal radionuclide uptake from bone scans and to evaluate the risk of pathological fracture, and is recommended as an initial imaging study in patients with bone pain.
Invasive Breast Cancer: Types, Symptoms, Treatment, Outlook
MRI or combined PET-CT may be considered for cases of abnormal radionuclide uptake during bone scan, in which radiography does not provide clear results.
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