News Releases & Research Results Elucidation of the mechanism of cancer progression induced by a factor from vascular endothelial cells in tumor tissues - Development of novel therapies targeting the signals of cancer microenvironment networks -

The results of collaborative research conducted by Professor Tetsuro Watabe and Lecturer Yasuhiro Yoshimatsu (currently Niigata University) of the Department of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Professor Kohei Miyazono and Mr. Yuichi Akatsu (currently Nippon Kayaku Co., Ltd.) of the Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo; and Professor Kyoko Hida of the Department of Oral Pathology and Biology, Graduate School of Dental Medicine, Hokkaido University.

• A mechanism by which cancer-associated fibroblasts (CAFs) derived from vascular endothelial cells induce malignant transformation by secreting transforming growth factor β2 (TGF-β2)* was elucidated.
  *TGF-β2, a promotor of fibroblast transformation, is involved in cell differentiation and motility and plays an important role in various pathophysiological phenomena such as ontogeny and cancer invasion and metastasis.

• The malignant transformation effects of CAFs, which transdifferentiate from vascular endothelial cells upon stimulation with TGF-β and tumor necrosis factor α (TNF-α), could be suppressed by inhibiting TGF-β signals with a neutralizing antibody.
• The results of this research should facilitate the development of novel therapies targeting TGF-β that mediates the cancer microenvironment networks.

This research was conducted with the support of the Project for Cancer Research and Therapeutic Evolution (P-CREATE) by AMED.

The results of this research project were published online in the international science journal Cancer Science on July 11.

Yoshimatsu Y., et al. TNF-α enhances TGF-β-induced endothelial-to-mesenchymal transition via TGF-β signal augmentation Cancer Science
DOI：10.1111/cas.14455