The receptor tyrosine kinase Tie1 is expressed and activated in epithelial tumour cell lines

Abstract

Abstract. The receptor tyrosine kinase Tie1 is expressed primarily in vascular endothelial cells. The receptor has also been detected in epithelial tumours in breast, thyroid and gastric cancers and in tumour cell lines where it appears as a 45 kDa truncated receptor fragment. In this study, we show that in addition to truncated Tie1, breast and colon tumour cell lines express a full-length Tie1 holoreceptor. In contrast to the situation in endothelial cells, Tie1 truncation is not activated by phorbol esters and generation of truncated Tie1 does not occur via a metalloprotease-inhibitor sensitive mechanism. Examination of the phosphorylation status of Tie1 revealed both the holoreceptor and truncated receptor to be constitutively activated in MCF-7 cells. These data indicate that Tie1 expressed in epithelial tumour cell lines is present in holoreceptor and truncated forms, and in MCF-7 cells both forms are constitutively phosphorylated and competent to signal. Our findings suggest therefore that antiangiogenic strategies targeting the angiopoietin/Tie system in tumour microvasculature could also have additional direct effects on the tumour epithelial cells within those tumours in which there is also extravascular expression of the Tie1 receptor tyrosine kinase.

Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma

“…Tie-1 and Tie-2 comprise the Tie family of RTKs and share the angiopoietins as activating ligands. Tie-1 is typically expressed on vascular endothelium and has been implicated in tumor angiogenesis [40]. Expression of Tie-1 has been reported in breast, gastric, colon, and thyroid cancers, but constitutive activation has only been proven in a breast cancer cell line [40,41].…”

“…Tie-1 is typically expressed on vascular endothelium and has been implicated in tumor angiogenesis [40]. Expression of Tie-1 has been reported in breast, gastric, colon, and thyroid cancers, but constitutive activation has only been proven in a breast cancer cell line [40,41]. In a study of 135 patients with TC, Tie-1 immunoreactivity was observed in PTC and anaplastic TC but not FTC or follicular adenomas, and it was also noted that large tumors had decreased expression [41].…”

Intra and extravascular transmembrane signalling of angiopoietin‐1‐Tie2 receptor in health and disease

“…Also in gastric carcinoma, Ang‐2 was expressed not only in endothelial cells but also in cancer cells, suggesting an Ang‐2‐Tie2 extravascular signalling together with Ang‐1‐Tie2 signalling [130]. Tie1 is expressed and constitutively phosphorylated to induce downstream signals in cancer cells of the breast, thyroid and gastrointestinal tract and in tumour cell line [131]. There is very little information on Ang‐1‐Tie2 signalling in cancer, outside the vasculature.…”

Heterogeneity of vascular and progenitor cell compartments in tumours from MMTV-PyVmT transgenic mice during mammary cancer progression

“…2006). Tie1 mRNA expression is increased in breast tumours, and while Tie1 expression and activation have been reported in MCF‐7 and inflammatory human breast cancer cell lines in vitro (Rees et al. 2007) (Shirakawa et al.…”