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

Abstract

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 SQ20B, resulting in three SQ20B sublines, AH50 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 serum-free environment. We demonstrated that sublines EV and AH50 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 AH50 proliferation significantly diminished. AH20 cells did not proliferate at all. Depletion of AHSG also diminished cellular migration and invasion. TGF-β was examined to determine whether levels of the TGF-β binding AHSG influenced the effect of TGF-β on cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-β influenced SMAD and ERK 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.

A secretomic study on human hepatocellular carcinoma multiple drug-resistant cell lines

“…Moreover, we found that, by knocking down this expression, AHSG accelerates the migration process in HepG2 and BEL7402 but hardly affects cancer cell invasion. Associated with the link between the AHSG and TGF-β pathway reported by many previous studies (28)(29)(30), the results of the present study suggest that the manner in which AHSG affects the tumor behaviors of HCC may depend on the degree it acts on the TGF-β signaling pathway, a result that remains to be verified in future studies. Thus, through iTRAQ-based secretomic analysis, this study has shown that the upregulation of AHSG in the MDR cell line of HCC may be a predictive factor of chemotherapeutic drug resistance of HCC, and it may also play a vital role in HCC progression.…”

3q26‐29 Amplification in head and neck squamous cell carcinoma: a review of established and prospective oncogenes

“…However, metformin (which targets AMPK/mTORC1) is the first‐line therapeutic for T2D and has been found to improve the overall survival of HNSCC patients . Interestingly, HNSCC cells are unique in that they produce endogenous AHSG , a process also evident in nontumour tongue tissue.…”

“…A role in HNSCC is further supported by the observation that AHSG is important for cellular adhesion. Reduced AHSG expression results in a diminished capacity for migration and invasion , possibly by protecting the metalloproteinase MMP‐9 from autolytic degradation . Furthermore, loss of AHSG has been shown to delay tumourigenesis and progression of breast cancer, where AHSG −/− /PyMT mice had dramatically reduced tumour incidence, with the majority of null mice being tumour free at completion of the study .…”

Fetuin‐A (alpha 2HS glycoprotein) modulates growth, motility, invasion, and senescence in high‐grade astrocytomas

“…Tumor cells generally have less requirement for serum supplementation in their growth media . We previously reported that the proliferation of head and neck squamous cell carcinoma cells in serum‐free medium relied on the ectopic fetuin‐A synthesized by these cells . Interestingly, we have demonstrated that fetuin‐A is the major growth‐promoting constituent of fetal bovine serum, particularly for tumor cell growth .…”