The Tumor Microenvironment Contribution to Development, Growth, Invasion and Metastasis of Head and Neck Squamous Cell Carcinomas

Overview

Journal J Cancer

Specialty Oncology

Date 2013 Feb 7

PMID 23386906

Citations 149

Authors

Sittichai Koontongkaew

Affiliations

Soon will be listed here.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a complex tissue that contains tumor cells and the surrounding stroma, which is populated by different types of mesenchymal cells and the extracellular matrix (ECM). Collectively, they are referred to as the tumor microenvironment (TME). Recent studies have shown that TME has a more profound influence on the growth and metastasis of HNSCC than was previously appreciated. Because carcinoma-associated fibroblasts (CAFs) are frequently observed in the stroma of the tumor, this review focuses on the potential role of tumor-CAFs interactions in progression of HNSCC. Tumor-CAFs crosstalk enhances the production of growth factors, cytokines, chemokines, matrix metalloproteinases (MMPs), and inflammatory mediators, which eventually facilitates tumor growth. In fact, factors and cells that do not support tumor growth are usually down regulated or mitigated in TME. Therefore TME may determine the fate of the tumors at the site of invasion and metastasis. For tumor cells that survive at these sites, stromal activation may serve to establish a supportive tumor stroma, fostering the outgrowth of the metastatic cells. The concept of tumor-stromal interactions and microenvironmental niche has profound consequences in tumor growth and metastasis and therefore, it's understanding will open up new strategies for the diagnosis, prognosis and therapy of HNSCC.

Citing Articles

Harnessing State-of-the-Art Gene Therapy to Transform Oral Cancer Treatment.

Zhang W, Zhang Y, Yang X, Chai H Biochem Genet. 2025; .

PMID: 40067653 DOI: 10.1007/s10528-025-11078-3.

Introducing CELLBLOKS: a novel organ-on-a-chip platform allowing a plug-and-play approach towards building organotypic models.

Llabjani V, Siddique M, Macos A, Abouzid A, Hoti V, Martin F In Vitro Model. 2025; 1(6):423-435.

PMID: 39872618 PMC: 11756440. DOI: 10.1007/s44164-022-00027-8.

Bacterial Outer Membrane Vesicle (OMV)-Encapsulated TiO Nanoparticles: A Dual-Action Strategy for Enhanced Radiotherapy and Immunomodulation in Oral Cancer Treatment.

Kan S, Zhang L, Wang Y, Chiang C, Chen M, Huang S Nanomaterials (Basel). 2024; 14(24).

PMID: 39728581 PMC: 11678132. DOI: 10.3390/nano14242045.

Mitochondrial DNA is a sensitive surrogate and oxidative stress target in oral cancer cells.

Tan J, Dong X, Liu H PLoS One. 2024; 19(9):e0304939.

PMID: 39226291 PMC: 11371132. DOI: 10.1371/journal.pone.0304939.

ABCC1 Is a ΔNp63 Target Gene Overexpressed in Squamous Cell Carcinoma.

La Banca V, De Domenico S, Nicolai S, Gatti V, Scalera S, Maugeri M Int J Mol Sci. 2024; 25(16).

PMID: 39201428 PMC: 11354449. DOI: 10.3390/ijms25168741.

References

Rogers S, Harrington K, Rhys-Evans P, O-Charoenrat P, Eccles S . Biological significance of c-erbB family oncogenes in head and neck cancer. Cancer Metastasis Rev. 2005; 24(1):47-69. DOI: 10.1007/s10555-005-5047-1. View

Zeng Q, Li S, Chepeha D, Giordano T, Li J, Zhang H . Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling. Cancer Cell. 2005; 8(1):13-23. DOI: 10.1016/j.ccr.2005.06.004. View

el-Gazzar R, Macluskey M, Williams H, Ogden G . Vascularity and expression of vascular endothelial growth factor in oral squamous cell carcinoma, resection margins, and nodal metastases. Br J Oral Maxillofac Surg. 2005; 44(3):193-7. DOI: 10.1016/j.bjoms.2005.06.030. View

Kato K, Hara A, Kuno T, Kitaori N, Huilan Z, Mori H . Matrix metalloproteinases 2 and 9 in oral squamous cell carcinomas: manifestation and localization of their activity. J Cancer Res Clin Oncol. 2004; 131(6):340-6. DOI: 10.1007/s00432-004-0654-8. View

de Vicente J, Fresno M, Villalain L, Vega J, Hernandez Vallejo G . Expression and clinical significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in oral squamous cell carcinoma. Oral Oncol. 2005; 41(3):283-93. DOI: 10.1016/j.oraloncology.2004.08.013. View

Wang F, Arun P, Friedman J, Chen Z, Van Waes C . Current and potential inflammation targeted therapies in head and neck cancer. Curr Opin Pharmacol. 2009; 9(4):389-95. PMC: 2731001. DOI: 10.1016/j.coph.2009.06.005. View

Vu H, Sikora A, Fu S, Kao J . HPV-induced oropharyngeal cancer, immune response and response to therapy. Cancer Lett. 2009; 288(2):149-55. DOI: 10.1016/j.canlet.2009.06.026. View

Hinsley E, Hunt S, Hunter K, Whawell S, Lambert D . Endothelin-1 stimulates motility of head and neck squamous carcinoma cells by promoting stromal-epithelial interactions. Int J Cancer. 2011; 130(1):40-7. DOI: 10.1002/ijc.25968. View

Sobral L, Bufalino A, Lopes M, Graner E, Salo T, Coletta R . Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion of activin A. Oral Oncol. 2011; 47(9):840-6. DOI: 10.1016/j.oraloncology.2011.06.011. View

10.

Nikitakis N, Siavash H, Sauk J . Targeting the STAT pathway in head and neck cancer: recent advances and future prospects. Curr Cancer Drug Targets. 2004; 4(8):637-51. DOI: 10.2174/1568009043332736. View

11.

McCawley L, Matrisian L . Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol Med Today. 2000; 6(4):149-56. DOI: 10.1016/s1357-4310(00)01686-5. View

12.

Yao S, Fine J . Periodontitis and cancer...a link? A review of the recent literature. Compend Contin Educ Dent. 2010; 31(6):436-42. View

13.

Hynes N, MacDonald G . ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 2009; 21(2):177-84. DOI: 10.1016/j.ceb.2008.12.010. View

14.

Liu Z, Hartman Y, Warram J, Knowles J, Sweeny L, Zhou T . Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN-depleted head and neck cancer tumor cells. Mol Cancer Res. 2011; 9(8):1008-17. PMC: 3157557. DOI: 10.1158/1541-7786.MCR-11-0043. View

15.

DeClerck Y . Interactions between tumour cells and stromal cells and proteolytic modification of the extracellular matrix by metalloproteinases in cancer. Eur J Cancer. 2000; 36(10):1258-68. DOI: 10.1016/s0959-8049(00)00094-0. View

16.

Geiger T, Peeper D . Metastasis mechanisms. Biochim Biophys Acta. 2009; 1796(2):293-308. DOI: 10.1016/j.bbcan.2009.07.006. View

17.

Liotta L, Kohn E . The microenvironment of the tumour-host interface. Nature. 2001; 411(6835):375-9. DOI: 10.1038/35077241. View

18.

Kalyankrishna S, Grandis J . Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol. 2006; 24(17):2666-72. DOI: 10.1200/JCO.2005.04.8306. View

19.

Ogino T, Shigyo H, Ishii H, Katayama A, Miyokawa N, Harabuchi Y . HLA class I antigen down-regulation in primary laryngeal squamous cell carcinoma lesions as a poor prognostic marker. Cancer Res. 2006; 66(18):9281-9. DOI: 10.1158/0008-5472.CAN-06-0488. View

20.

van Houten V, Tabor M, van den Brekel M, Kummer J, Denkers F, Dijkstra J . Mutated p53 as a molecular marker for the diagnosis of head and neck cancer. J Pathol. 2002; 198(4):476-86. DOI: 10.1002/path.1242. View