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A Novel Endoglin Variant in Pancreatic Ductal Adenocarcinoma
Author(s) -
Kumar Sanjay,
Shah Nirav,
Zaman Naveed,
Lee Nam Y
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.934.22
Subject(s) - endoglin , pancreatic cancer , cancer research , paracrine signalling , angiogenesis , autocrine signalling , medicine , neovascularization , pancreas , cancer , pathology , biology , stem cell , receptor , genetics , cd34
Advanced pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive and lethal malignancies with poor long‐term prognosis. Although early diagnosis for surgical resection is considered essential for improved survival outcome, most patients have delayed presentation of signs and symptoms until the disease has advanced or metastasized. Hence, significant improvements in treatment options will require a greater understanding of PDAC progression at the molecular level along with identification of new therapeutic targets and associated biomarkers. Endoglin is a TGF‐b co‐receptor essential for normal and tumor angiogenesis. Its expression is generally restricted to proliferating vascular endothelial cells (ECs) during neovascularization, although more recently endoglin expression has been found in a subset of breast, prostate and pancreatic tumors. While the functional roles of endoglin in tumors are still emerging, here we report a unique PDAC‐specific endoglin isoform (PDAC‐Eng) not expressed in normal human pancreatic ductal epithelia or ECs. We provide evidence that PDAC‐Eng is a novel splice variant and not a proteolytic byproduct. Additionally, PDAC‐Eng is secreted as an unexpected component of PDAC exosomes, which we found exerts strong autocrine and paracrine effects by enhancing endothelial and PDAC cell growth inhibition and deregulates TGF‐b signaling. Taken together, these findings support endoglin as a potentially new prognostic marker and a therapeutic target in pancreatic cancer.