Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer
| Autor: | Hua Zhou, John R. Basile, Amr Bugshan, Asma Buhamrah, Yi-Ling Lin, Ying-Hua Yang, Abraham Schneider |
|---|---|
| Přispěvatelé: | Zhang, Chi |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology Physiology lcsh:Medicine Osteoclasts Semaphorins Metastasis Bone remodeling Mice 0302 clinical medicine Animal Cells Breast Tumors Basic Cancer Research Medicine and Health Sciences 2.1 Biological and endogenous factors MC3T3 Enzyme-Linked Immunoassays Aetiology Neoplasm Metastasis lcsh:Science Connective Tissue Cells Cancer Multidisciplinary Tumor Cell Differentiation Osteoblast Animal Models Osteoblast Differentiation 3. Good health Neoplasm Proteins CD medicine.anatomical_structure Oncology Connective Tissue 030220 oncology & carcinogenesis Heterografts Female Bone Remodeling Cellular Types Anatomy Research Article medicine.medical_specialty General Science & Technology SEMA4D Mouse Models Bone Neoplasms Breast Neoplasms Biology Research and Analysis Methods Bone resorption Cell Line Calcification 03 medical and health sciences Model Organisms Calcification Physiologic Semaphorin Antigens CD Osteoclast Cell Line Tumor Breast Cancer medicine Animals Humans Bone Resorption Antigens Bone Immunoassays Physiologic Osteoblasts lcsh:R Interleukin-8 Biology and Life Sciences Cancers and Neoplasms Cell Biology medicine.disease Biological Tissue 030104 developmental biology Musculoskeletal Immunologic Techniques Cancer research lcsh:Q Physiological Processes Neoplasm Transplantation Developmental Biology |
| Zdroj: | PloS one, vol 11, iss 2 PLoS ONE PLoS ONE, Vol 11, Iss 2, p e0150151 (2016) |
| Popis: | Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D) as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption. Breast cancers and other epithelial malignancies overexpress Sema4D, so we theorized that tumor cells could be exploiting this pathway to establish lytic skeletal metastases. Here, we use measurements of osteoblast and osteoclast differentiation and function in vitro and a mouse model of skeletal metastasis to demonstrate that both soluble Sema4D and protein produced by the breast cancer cell line MDA-MB-231 inhibits differentiation of MC3T3 cells, an osteoblast cell line, and their ability to form mineralized tissues, while Sema4D-mediated induction of IL-8 and LIX/CXCL5, the murine homologue of IL-8, increases osteoclast numbers and activity. We also observe a decrease in the number of bone metastases in mice injected with MDA-MB-231 cells when Sema4D is silenced by RNA interference. These results are significant because treatments directed at suppression of skeletal metastases in bone-homing malignancies usually work by arresting bone remodeling, potentially leading to skeletal fragility, a significant problem in patient management. Targeting Sema4D in these cancers would not affect bone remodeling and therefore could elicit an improved therapeutic result without the debilitating side effects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|