Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth

International Journal of Molecular Sciences

Paolo Meda¹  Tania Santoro²  Lauriane Hamard²  Jacques-Antoine Haefliger²  Denise Nardelli-Haefliger³  Valérie Cesson³  Karthik Sathiyanadan³  Sonia Domingos-Pereira³  Florian Alonso⁴ 

[1] Department of Cell Physiology and Metabolism, Medical Center, University of Geneva, 1206 Geneva, Switzerland;Department of Medicine, Lausanne University Hospital, 1011 Lausanne, Switzerland;Department of Urology, Lausanne University Hospital, 1011 Lausanne, Switzerland;Laboratory for the Bioengineering of Tissues (BioTis-INSERM U1026), Université de Bordeaux, 33607 Bordeaux, France;

关键词: cell-cell communication;    connexins;    angiogenesis;    tumors;    transgenic mice;   

DOI  :  10.3390/ijms23062930

来源: DOAJ

【 摘 要 】

Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments.

【 授权许可】

Unknown