Volume 14 Supplement 17
The α2-HeremansSchmid glycoprotein (AHSG) promotes growth in head and neck squamous cell carcinoma (HNSCC)
© Thompson et al; licensee BioMed Central Ltd. 2013
Published: 22 October 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.
SQ20B-WT, -EV, -AH50 and -AH20 cell lines were evaluated for properties associated with proliferation, migration and invasion. All cell lines were compared to SQ20B-WT
p < 0.05
p < 0.05
p < 0.05
p < 0.009
p < 0.009
Top biofunctions calculated (Ingenuity Pathways Analysis) from gene list generated by comparison of SQ20B-AH20 and SQ20B-WT for genes differentially expressed at p< 0.05 (Benjamini and Hochberg multiple testing correction) and fold difference ≥1.5
Diseases and Disorders
Dermatological Diseases and Conditions
2.00E-08 – 1.47E-02
1.90E -07 – 1.55E-02
Reproductive System Disease
2.31E -07 – 1.48E-02
Endocrine System Disorders
3.17E-07 – 2.29E-03
7.32E-06 – 1.62E-02
Molecular and Cellular Functions
5.75E-06 – 1.62E-02
6.04E-05 – 1.47E-02
6.04E-05 – 1.59E-02
Small Molecule Biochemistry
6.04E-05 – 1.51E-02
Cell-To-Cell Signaling and Interaction
8.26E-05 – 1.59E-02
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.
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.
- Guillory B, Sakwe AM, Saria M, Thompson P, Adhiambo C, Koumangoye R, Ballard B, Binhazim A, Cone C, Jahanen-Dechent W, Ochieng J: Lack of fetuin-A (alpha2-HS-glycoprotein) reduces mammary tumor incidence and prolongs tumor latency via the transforming growth factor-beta signaling pathway in a mouse model of breast cancer. Am J Pathol. 2010, 177 (5): 2635-2644. 10.2353/ajpath.2010.100177.PubMed CentralView ArticlePubMedGoogle Scholar
- Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W: The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest. 2003, 112 (3): 357-366.PubMed CentralView ArticlePubMedGoogle Scholar
- Swallow CJ, Partridge EA, Macmillan JC, Tajirian T, DiGuglielmo GM, Hay K, Szweras M, Jahnen-Dechent W, Wrana JL, Redston M, Gallinger S, Dennis JW: alpha2HS-glycoprotein, an antagonist of transforming growth factor beta in vivo, inhibits intestinal tumor progression. Cancer Res. 2004, 64 (18): 6402-6409. 10.1158/0008-5472.CAN-04-1117.View ArticlePubMedGoogle Scholar
- Brown WM, Dziegielewska KM, Saunders NR, Christie DL, Nawratil P, Müller-Esterl W: The nucleotide and deduced amino acid structures of sheep and pig fetuin. Common structural features of the mammalian fetuin family. Eur J Biochem. 1992, 205 (1): 321-331. 10.1111/j.1432-1033.1992.tb16783.x.View ArticlePubMedGoogle Scholar
- Kundranda MN, Henderson M, Carter KJ, Gorden L, Binhazim A, Ray S, Baptiste T, Shokrani M, Leite-Browning ML, Jahnen-Dechent W, Matrisiann LM, Ochieng J: The serum glycoprotein fetuin-A promotes Lewis lung carcinoma tumorigenesis via adhesive-dependent and adhesive-independent mechanisms. Cancer Res. 2005, 65 (2): 499-506.PubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.