Reactive Astrocytes Protect Melanoma Cells from Chemotherapy by Sequestering Intracellular Calcium through Gap Junction Communication Channels
Autor: | Isaiah J. Fidler, Krishnakumar Balasubramanian, Lixia Guo, Menashe Bar-Eli, Kenneth Aldape, Qingtang Lin, Dominic Fan, Hua Wang, Sun Jin Kim |
---|---|
Rok vydání: | 2010 |
Předmět: |
Intracellular Fluid
Male Cancer Research Cell signaling Drug Evaluation Preclinical Mice Nude Antineoplastic Agents Mice Transgenic Cell Communication Blood–brain barrier Neuroprotection Models Biological lcsh:RC254-282 Calcium in biology Connexins 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor medicine Animals Humans Cells Cultured 030304 developmental biology 0303 health sciences Glial fibrillary acidic protein biology Melanoma Gap junction medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology medicine.anatomical_structure Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis Astrocytes biology.protein NIH 3T3 Cells Calcium Research Article |
Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 12, Iss 9, Pp 748-754 (2010) |
ISSN: | 1476-5586 |
DOI: | 10.1593/neo.10602 |
Popis: | Brain metastases are highly resistant to chemotherapy. Metastatic tumor cells are known to exploit the host microenvironment for their growth and survival. We report here that melanoma brain metastases are surrounded and infiltrated by activated astrocytes, and we hypothesized that these astrocytes can play a role similar to their established ability to protect neurons from apoptosis. In coculture experiments, astrocytes, but not fibroblasts, reduced apoptosis in human melanoma cells treated with various chemotherapeutic drugs. This chemoprotective effect was dependent on physical contact and gap junctional communication between astrocytes and tumor cells. Moreover, the protective effect of astrocytes resulted from their sequestering calcium from the cytoplasm of tumor cells. These data suggest that brain tumors can, in principle, harness the neuroprotective effects of reactive astrocytes for their own survival and implicate a heretofore unrecognized mechanism for resistance in brain metastasis that might be of relevance in the clinic. |
Databáze: | OpenAIRE |
Externí odkaz: |