Angiopoietin-Like Proteins in Angiogenesis, Inflammation and Cancer

Abstract

Altered expression of secreted factors by tumor cells or cells of the tumor microenvironment is a key event in cancer development and progression. In the last decade, emerging evidences supported the autocrine and paracrine activity of the members of the Angiopoietin-like (ANGPTL) protein family in angiogenesis, inflammation and in the regulation of different steps of carcinogenesis and metastasis development. Thus, ANGPTL proteins become attractive either as prognostic or predictive biomarkers, or as novel target for cancer treatment. Here, we outline the current knowledge about the functions of the ANGPTL proteins in angiogenesis, cancer progression and metastasis. Moreover, we discuss the most recent evidences sustaining their role as prognostic or predictive biomarkers for cancer therapy. Although the role of ANGPTL proteins in cancer has not been fully elucidated, increasing evidence suggest their key effects in the proliferative and invasive properties of cancer cells. Moreover, given the common overexpression of ANGPTL proteins in several aggressive solid tumors, and their role in tumor cells and cells of the tumor microenvironment, the field of research about ANGPTL proteins network may highlight new potential targets for the development of future therapeutic strategies.

Mapping the O‐glycoproteome using site‐specific extraction of O‐linked glycopeptides (EXoO)

“…This type of fine‐tuning of the ECM network might be critical to supporting tumorigenesis and tumor progression (Lu et al , ). In addition, carbonic anhydrase 9 (CA9) and angiopoietin‐related protein 4 (ANGPTL4), proteins known to respond to tumor hypoxia (Sedlakova et al , ; Carbone et al , ), showed 13‐ and 3.6‐fold increases, respectively, in tumor tissue (Fig D and Appendix Table S1). Finally, EGF‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1), which binds to epidermal growth factor receptor (EGFR) to promote tumor growth, invasion, and metastasis (Yin et al , ), showed a threefold increase across seven O‐linked glycosylation sites in tumor tissue (Fig D and Appendix Table S1).…”

Correlation of circulating ANGPTL5 levels with obesity, high sensitivity C-reactive protein and oxidized low-density lipoprotein in adolescents

“…Angiopoietin-like protein 5 (ANGPTL5) is a member of the angiopoietin-like proteins (ANGPTLs) family. Eight members have been described so far (ANGPTL1 through ANGPTL8), and have been shown to have various physiological functions in lipid and glucose metabolism, inflammation, hematopoiesis, angiogenesis and cancer [4][5][6][7] . They are also differentially expressed in multiple tissues: for example, while ANGPTL3 is exclusively expressed in the liver and kidney, ANGPTL7 is expressed in the eye.…”

“…Other members such as ANGPTL2 and ANGPTL4 are more ubiquitously expressed. ANGPTL5, on the other hand, was mainly shown to be expressed in adipose tissue, but it was also detected at lower levels in the heart, ovary, testis and skin 5,6,8,9 . ANGPTLs were thought to be orphan ligands until a study showed that ANGPTL1, 2, 5 and 7 can bind to the immune-inhibitory receptor human leukocyte immunoglobulin-like receptor B2 10 .…”

Mapping In Vivo O-Glycoproteome Using Site-specific Extraction of O-linked glycopeptides (EXoO)

“…This type of fine-tuning of the ECM network is known to be critical to supporting tumorigenesis and tumor progression 31 . In addition, carbonic anhydrase 9 (CA9) and angiopoietin-related protein 4 (ANGPTL4), proteins known to respond to tumor hypoxia 32 , 33 , showed 13 and 3.6-fold increases respectively in tumor tissue (Fig. 3D and Supplementary table 6).…”