The α2-HeremansSchmid glycoprotein (AHSG) promotes growth in head and neck squamous cell carcinoma (HNSCC)
BMC Bioinformatics volume 14, Article number: A7 (2013)
AHSG is a calcium-binding glycoprotein synthesized primarily by the liver [1–3] and secreted into serum [1–3]. Primarily known for its role in bone growth and remodeling, it is also reported to be involved in the progression of breast and lung cancer with these cells utilizing the liver synthesized form [1, 4, 5]. Uniquely, HNSCC cells synthesize their own AHSG, suggesting autocrine signaling fueling cell proliferation and movement. Here we present data showing the presence of AHSG mRNA in HNSCC cell line SQ20B and phenotypic and transcriptomic changes resulting from shRNA knockdown of AHSG protein expression.
Materials and methods
HNSCC cell line SQ20B was transduced with pGIPZ empty vector or pGIPZ with different AHSG target sequences to generate AHSG deficient cell lines. Depletion of AHSG was confirmed by immunoblot using Meridian AHSG polyclonal antibody and immunocytochemical staining for vector-encoded GFP. To evaluate the physiological loss of AHSG on cell biology, cells were cultured in serum free-media, as serum is a source of AHSG in all animals. Proliferation, migration and invasion were evaluated using standard methodologies. Transcriptomic analysis of cell lines was performed using the Affymetrix Human Gene 2.0 ST chip.
The role of AHSG in cell proliferation, invasion and migration was evaluated for wildtype SQ20B (SQ20B-WT), SQ20-B with empty vector (SQ20B-EV), SQ20B expressing 50% or 20% of AHSG expressed by SQ20B-EV (SQ20B-AH50 and –AH20 respectively). Decreased AHSG expression resulted in decreased proliferation, migration and invasion of SQ20B cells (Table 1).
Transcriptomic analysis identified genes associated with cancer and cellular movement as two of the top biofunction categories associated with AHSG molecular function.
AHSG affects in vitro cellular properties associated with metastatic potential in vivo. Transcriptomic analysis has identified highly relevant transcriptomic programs of expression that will highlight new cellular processes that are likely associated with metastasis of HNSCC.
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This work was supported by grants from the SC1 CA134018-01 (JO); DOD W81XWH-07-1-0254 (JO); and U54 CA091408 (subproject DM). PT supported in part by the Vanderbilt CTSA grant UL1 TR000445 from NCRR/NIH; and 5 T32 HL007735-15.
Microarray processed at Vanderbilt University Genomic Science Resource Core, Nashville, TN, 37208.
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Thompson, P.D., Sakwe, A., Ochieng, J. et al. The α2-HeremansSchmid glycoprotein (AHSG) promotes growth in head and neck squamous cell carcinoma (HNSCC). BMC Bioinformatics 14 (Suppl 17), A7 (2013). https://doi.org/10.1186/1471-2105-14-S17-A7