Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

作者：Thompson Pamela D; Sakwe Amos; Koumangoye Rainelli; Yarbrough Wendell G; Ochieng Josiah; Marshall Dana R^*

来源：Experimental Cell Research, 2014, 321(2): 123-132.

DOI：10.1016/j.yexcr.2013.12.003

• AHSG
• HNSCC
• TGF-beta
• MMP-9
• Adhesion
• Metastasis
• Migration
• Invasion

This study was performed to identify the potential role of Alpha-2 Heremans Schmid Glycoprotein (AHSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) tumorigenesis using an HNSCC cell line model. HNSCC cell lines are unique among cancer cell lines, in that they produce endogenous AHSG and do not rely, solely, on AHSG derived from serum. To produce our model, we performed a stable transfection to down-regulate AHSG in the HNSCC cell line SQ2013, resulting in three SQ2013 sublines, AHSO with 50% AHSG production, AH20 with 20% AHSG production and EV which is the empty vector control expressing wild-type levels of AHSG. Utilizing these sublines, we examined the effect of AHSG depletion on cellular adhesion, proliferation, migration and invasion in a serumfree environment. We demonstrated that sublines EV and AHSO adhered to plastic and laminin significantly faster than the AH20 cell line, supporting the previously reported role of exogenous AHSG in cell adhesion. As for proliferative potential, EV had the greatest amount of proliferation with AHSO proliferation significantly diminished. AH20 cells did not proliferate at all. Depletion of AHSG also diminished cellular migration and invasion. TGF-beta was examined to determine whether levels of the TGF-beta binding AHSG influenced the effect of TGF-beta on cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-beta influenced SMAD and ERIC signaling, it did not clearly affect proliferation, suggesting that AHSG influences on adhesion, proliferation, invasion and migration are primarily due to its role in adhesion and cell spreading. The previously reported role of AHSG in potentiating metastasis via protecting MMP-9 from autolysis was also supported in this cell line based model system of endogenous AHSG production in HNSCC. Together, these data show that endogenously produced AHSG in an HNSCC cell line, promotes in vitro cellular properties identified as having a role in tumorigenesis.

• 出版日期2014-2-15