Bathe, Oliver F.Opoku-Darko, Michael2017-12-182017-12-182008Opoku-Darko, M. (2008). Tumor endothelial marker 8 (TEM8) expression in tumor and endothelial cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/2214http://hdl.handle.net/1880/103215Bibliography: p. 91-109Tumor endothelial marker 8 (TEM8) is highly expressed in tumor vasculature, but not in other endothelial cells including those involved in normal physiological angiogenesis such as wound healing and corpus luteum formation. It has not been reported whether this is due to some intrinsic characteristic of the tumor endothelium or secondary to tumor microenvironmental factors. Screening of TEM8 levels in various cancer and endothelial cell lines used in this project revealed variable transcript level. Changes in level of expression of TEM8 transcripts in human umbilical vein endothelial cells (HUVECs) were examined under the influence of such microenvironmental factors as hypoxia and vascular endothelial growth factor (VEGF), the most potent pro-angiogenic agent. While hypoxia dramatically increased the levels of TEM8 in HUVECs, VEGF seemed to do so only moderately. TEM8 mRNA levels were elevated in HUVECs co­cultured with some breast cancer cell lines including, Hs578T, MDA MB 468, MDA MB 453s, MDA MB 231 and MDA MB 436. Contrary to that however, HUVECs co-cultured with the breast cancer cell lines, SKBR3, MCF-7 and BT-474 had no significant changes in TEM8 transcription. Induction of TEM8 was due to direct cell-cell contact rather than to secretion of soluble factors by the tumor cells. Interestingly, the TEM8 inducing breast cancer cell lines have a more aggressive phenotype than the non-inducing group. TEM8 may therefore be a marker of aggressiveness in breast cancer. Overexpression of TEM8 in HUVECs led to more rapid endothelial cell growth and, in contrast down-regulating the gene by AdshRNA resulted in reduced cell growth. Together, these data suggest that endothelial cell expression of TEM8 is a function of the tumor microenvironment. Its up­regulation in tumor-associated endothelial cells encourages their growth.xi, 97 leaves : ill. ; 30 cm.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.master thesis10.11575/PRISM/2214