TGF-β Signal Disruption Linked to Faster Cancer Growth
Study looks at diffuse-type gastric carcinoma in mice; disease has poor prognosis in humans
TUESDAY, May 5 (HealthDay News) -- In mice, disruption of transforming growth factor β (TGF-β) signaling may encourage the growth of diffuse-type gastric carcinoma, according to research published in the April 15 issue of the Journal of the National Cancer Institute.
Akiyoshi Komuro, Ph.D, of the University of Tokyo, and colleagues discuss their work in expressing a dominant-negative TGF-β type II receptor (dnTβRII) in two diffuse-type gastric carcinoma cell lines to disrupt TGF-β signaling, which were injected into mice either subcutaneously or into the gastric wall. The authors also caused cells to express the angiogenic inhibitor thrombospondin-1 via a lentiviral infection system.
The researchers found that expression of dnTβRII in OCUM-2MLN carcinoma cells didn't influence their proliferation in vitro, but did speed the growth of transplanted tumors in vivo. Tumors expressing dnTβRII showed more angiogenesis than controls, due to less production of thrombospondin-1. The other type of cells (OCUM-12) showed similar results, the authors note.
"In conclusion, we have shown that disruption of TGF-β signaling in a mouse model of diffuse-type gastric carcinoma, which may be analogous to what occurs during progression of this disease in humans, promotes tumorigenesis by accelerating angiogenesis. Because the loss of TβRII or Smad4 expression has been reported to induce tumor angiogenesis in other types of cancers, the administration of angiogenesis inhibitors, including sorafenib and thrombospondin-1 analogues, may be useful as a treatment for those cancers with disrupted TGF-β signaling pathways," the authors write.