Endoglin Expression in Non-tumor and Tumor Cells of Different Origin

Abstract

The transmembrane protein endoglin (CD105) is a component of the receptor complex for TGF-β family growth factors. It is expressed primarily in endothelial cells, mesenchymal stromal cells, and early hematopoietic precursors. The density of CD105 on the membrane of endothelial cells increases upon their proliferation. A soluble endoglin form (sEng) is produced by a cleavage of an extracellular fragment from CD105, performed by the matrix metalloproteinase MMP-14. sEng blood level serves as an indicator of angiogenesis during the progression of some tumors. The contribution of tumor cells into the sEng pool remains unknown. We investigated the expression of CD105, production of sEng, as well as the mRNA level of two splice-variants of endoglin and mmp-14 genes using a collection of 43 cultures of tumorous and normal cells of different histological origin. Over half of the tumor cell lines and normal stromal cells contained cell populations expressing the membrane-bound endoglin. Cytoplasmic endoglin with unknown function was found in cells of three tumor lines. In all cell cultures, the mRNA expression of L-endoglin splice-variant prevailed over the expression of S-endoglin. We have investigated, for the first time, the formation of sEng in the stromal and tumor cells, and revealed the endothelial cells as the main source of sEng. Normal stromal cells and the majority of CD105+ tumor cells produce only low levels of sEng. Among the tumor cell lines, the highest sEng production was detected in the MeWo melanoma cells, that are characterized by the highest activity of mmp-14 gene.