Tumor Endothelial Marker 8 Overexpression in Breast Cancer Cells Enhances Tumor Growth and Metastasis

Abstract

Tumor vasculature is known to express high levels of the longest splice variant of tumor endothelial marker 8 (TEM8). Little is known about its expression by tumor cells. Five of eight cell breast cancer cell lines tested expressed significant levels of the longest TEM8 splice variant (TEM8.1), and to a lesser extent, the shortest splice variant (TEM8.3). Breast cancer cell lines expressing high levels of TEM8 are known to be more invasive and typify a more aggressive basal-like phenotype. In vivo studies in the 4T1 murine model showed enhanced tumor growth associated with increased tumor vascularity and metastasis to lymph nodes and lungs. These data suggest that TEM8.1 expression in breast cancer cells confers a more aggressive, proangiogenic phenotype.

Tumor endothelial marker 8 promotes cancer progression and metastasis

“…TEM8 was shown to be a functional marker for cancer stem cells in breast cancer, by activating Wnt signaling and by acting in a signaling network with collagen VI, impacting breast cancer stem cell characteristics and metastatic potential by positively regulating tumor growth [ 20 ]. TEM8 was associated with a more invasive and aggressive phenotype in breast cancer [ 20 ] and was found to be upregulated in invasive breast cancer [ 3 ]. Furthermore, we found that TEM8 expression is higher in tumors compared to normal tissue in both breast cancer and colon cancer patient samples.…”

“…Metastasis, the spread of cancer to distant sites, accounts for 90% of these deaths. A promising target for blocking tumor progression, without causing severe side effects [ 2 ], is Tumor Endothelial Marker 8 (TEM8), an integrin-like cell surface protein expressed predominantly in the tumor endothelium and in cancer cells [ 3 , 4 ]. Here, we have investigated the role of TEM8 in cancer progression, angiogenesis and metastasis in invasive breast cancer, and validated the main findings and important results in colorectal cancer.…”

TEM8 specific T cells target the tumor cells and tumor-associated vasculature in triple negative breast cancer

“…as one of nine gene products preferentially upregulated in the tumor-associated vs. normal endothelium [ 1 ]. Interestingly, TEM8 has also been identified as a tumor restricted antigen in triple negative breast cancers (TNBC) [ 2 , 3 ]; a clinical entity associated with a particularly poor prognosis. Being null for HER2, estrogen and progesterone receptors, targeted therapies for TNBC are quite limited.…”

Identification of Small Molecules That Inhibit the Interaction of TEM8 with Anthrax Protective Antigen Using a FRET Assay

“…Further, missense mutations in the TEM8 gene have been identified in individuals with infantile hemangioma, a disease characterized by localized lesions of disorganized angiogenesis 14 . More recent studies have suggested that the level of TEM8 expression within breast cancer cell lines is correlated with their capacity for growth, invasion, and metastasis, with more aggressive basal-like cells expressing higher levels of TEM8 mRNA and protein 15 . The link between TEM8 and tumorigenesis has also led to interest in manipulating the tumor-specific expression of TEM8 for the selective delivery of toxic or vascular-disrupting agents to tumor sites 16 .…”