4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Clinical and Biological Implications of the Tumor Microenvironment

      Cancer Microenvironment
      Springer Nature

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Related collections

          Most cited references44

          • Record: found
          • Abstract: found
          • Article: not found

          Matricellular proteins: extracellular modulators of cell function.

          The term 'matricellular' has been applied to a group of extracellular proteins that do not contribute directly to the formation of structural elements in vertebrates but serve to modulate cell-matrix interactions and cell function. Our understanding of the mode of action of matricellular proteins has been advanced considerably by the recent elucidation of the phenotypes of mice that are deficient in these proteins. In many cases, aspects of these phenotypes have illuminated previously unsuspected consequences of the lack of appropriate interactions of cells with their environment.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer.

            The microenvironment is known to critically modulate tumor progression, yet its role in regulating treatment response is poorly understood. Here we found increased macrophage infiltration and cathepsin protease levels in mammary tumors following paclitaxel (Taxol) chemotherapy. Cathepsin-expressing macrophages protected against Taxol-induced tumor cell death in coculture, an effect fully reversed by cathepsin inhibition and mediated partially by cathepsins B and S. Macrophages were also found to protect against tumor cell death induced by additional chemotherapeutics, specifically etoposide and doxorubicin. Combining Taxol with cathepsin inhibition in vivo significantly enhanced efficacy against primary and metastatic tumors, supporting the therapeutic relevance of this effect. Additionally incorporating continuous low-dose cyclophosphamide dramatically impaired tumor growth and metastasis and improved survival. This study highlights the importance of integrated targeting of the tumor and its microenvironment and implicates macrophages and cathepsins in blunting chemotherapeutic response.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Gap junction-mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells.

              Bone marrow (BM) metastasis of breast cancer (BC) can recur even decades after initial diagnosis and treatment, implying the long-term survival of disseminated cancer cells in a dormant state. Here we investigated the role of microRNAs (miRNA) transmitted from BM stroma to BC cells via gap junctions and exosomes in tumor cell quiescence. MDA-MB-231 and T47D BC cells arrest in G(0) phase of the cell cycle when cocultured with BM stroma. Analyses of miRNA expression profiles identified numerous miRNAs implicated in cell proliferation including miR-127, -197, -222, and -223 targeting CXCL12. Subsequently, we showed that these CXCL12-specific miRNAs are transported from BM stroma to BC cells via gap junctions, leading to reduced CXCL12 levels and decreased proliferation. Stroma-derived exosomes containing miRNAs also contributed to BC cell quiescence, although to a lesser degree than miRNAs transmitted via gap junctions. This study shows that the transfer of miRNAs from BM stroma to BC cells might play a role in the dormancy of BM metastases. ©2011 AACR.
                Bookmark

                Author and article information

                Journal
                Cancer Microenvironment
                Cancer Microenvironment
                Springer Nature
                1875-2292
                1875-2284
                August 2012
                February 3 2012
                August 2012
                : 5
                : 2
                : 95-112
                Article
                10.1007/s12307-012-0099-6
                5d356e2e-a690-4a89-bd32-2a514b14c38a
                © 2012
                Product
                Self URI (article page): http://link.springer.com/10.1007/s12307-012-0099-6

                Comments

                Comment on this article