Suppression of cancer phenotypes through a multifunctional actin-binding protein, calponin, that attacks cancer cells and simultaneously protects the host from invasion.
Quantitative and/or qualitative alteration of actin cytoskeletal molecules, involved in the regulation of cellular dynamic functions, should be intimately related with cancer phenotypes. Based on several lines of experimental evidence from our group, and others, this report proposes a strategy to simultaneously attack cancer cells and protect the host from cancer invasion, with one molecule. Calponin h1, an actin-stabilizing protein that is also intimately related to signal transduction, is very often suppressed in vascular smooth muscle cells of malignant human tumors and in mesothelial cells by coexisting cancer cells. We generated mice deficient for calponin h1, exhibiting fragility in blood vessels and peritoneal membranes. Hematogenous cancer metastasis occurred more easily in the calponin h1-deficient mice than in wild-type mice, and the peritoneal dissemination was extremely enhanced. The fragility was rescued by the exogenous introduction of the calponin h1 gene into mesothelial cells of the peritoneum. Furthermore, calponin h1 gene transfer into several transformed cell lines resulted in a suppression of malignancy. The peritoneal dissemination of intraperitoneally-injected B16-F10 cells was suppressed by the calponin h1 gene, given to target both cancer cells and the mesothelial cells of the host. The multifunctional nature of the molecule, as a machinery player of cytoskeleton and mediator of signal transduction, probably resulted in a favorable recipient-discriminating effect on cancerous and normal cells. Thus, we believe that if we use adequate multifunctional molecules for therapy, it is possible to simultaneously suppress cancer phenotypes and protect normal cells from the attack of cancer cells.
Taniguchi
Shun'ichiro
S
Department of Molecular Oncology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan. stangch@sch.md.shinshu-u.ac.jp
D000818:Animals; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D018890:Chemoprevention; D003598:Cytoskeletal Proteins / Q000502:physiology; D015536:Down-Regulation; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009361:Neoplasm Invasiveness / Q000503:physiopathology / Q000517:prevention & control*; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental; D009389:Neovascularization, Pathologic; D010641:Phenotype; D015398:Signal Transduction; D000096985:Calponins
D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D000096985:Calponins; C402202:PYCARD protein, human