Identification of IGPR-1 as a Novel Cell Adhesion Molecule Involved in Tumor Growth and Angiogenesis
Manisha N Mehta, Rosana D Meyer, John E Mahoney, Kobra Rezazedeh, Nader Rahimi. Boston University School of Medicine, Boston, MA
Background: Pathological angiogenesis is a hallmark step in tumor growth and metastasis. We have identified IGPR-1 (Immunoglobulin containing and Proline rich Receptor-1) gene as a novel cell adhesion molecule which regulates tumor growth and angiogenesis.
Design: IGPR-1 expression and its cellular functions were determined by molecular, cellular and biochemical assays, immunohistochemistry, immunofluorescence microscopy, qPCR, Western blot, in vivo and in vitro angiogenesis assays.
PAE cells [A] expressing empty vector [B], IGPR-1 alone [C] or IGPR-1 with VEGFR-2 [D] were subjected to matrigel assay and angiogenesis compared. HUVEC cells transfected with control siRNA [E] or IGPR-1 siRNA [F] were subjected to matrigel assay and angiogenesis compared. Expression of IGPR-1 in HUVEC cells [G] was compared with protein loading control [H]. B16F cells expressing empty vector or IGPR-1 were mixed with matrigel, injected under mice skin and growth compared [I]. Expression of IGPR-1 in B16F cells shown [J-K].
Results: IGPR-1 transcript was detected in variable levels in human artery, bone marrow, brain, vein, lung and liver. IGPR-1 undergoes cis and trans-dimerization and regulates cellular morphology and cell-cell interaction. Silencing expression of IGPR-1 and ectopic over-expression showed that IGPR-1 regulates angiogenesis in vivo and in vitro. Immunohistochemical expression of IGPR-1 was detected in normal human lung (A)and lung tumors- adenocarcinoma [B], small cell carcinoma [C] and squamous cell carcinoma [D].
Conclusions: IGPR-1 is expressed mainly by epithelial and endothelial cells. IGPR-1 stimulates focal adhesion, actin fibril formation and angiogenesis in vivo and in vitro. Importantly, IGPR-1 expression is elevated in certain tumors suggesting that IGPR-1 may play a distinct role in neoplasia development.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 257, Wednesday Morning