HSP70 induces TLR4 signaling in oral squamous cell carcinoma: an immunohistochemical study

• Published in: Journal of cancer research and therapeutics 2013-10, Vol.9 (4), p.624-629
• Main Authors: Nair, Sindhu, Kotrashetti, Vijayalakshmi S, Nayak, Ramakant, Bhat, Kishore, Somannavar, Pradeep, Hosmani, Jagadish
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Cancer; Carcinoma, Squamous Cell - pathology; Cell growth; Cytokines; Female; Head and Neck Neoplasms - pathology; Heat shock proteins; HSP70 Heat-Shock Proteins - biosynthesis; HSP70 Heat-Shock Proteins - immunology; Humans; Identification and classification; Immune system; Immunity, Innate; Immunohistochemistry; Kinases; Male; Middle Aged; Mortality; Mouth cancer; Mouth Neoplasms - pathology; Myeloid Differentiation Factor 88; Oncology, Experimental; Pilot Projects; Properties; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Staining and Labeling; Toll-Like Receptor 4 - agonists; Toll-Like Receptor 4 - biosynthesis; Toll-Like Receptor 4 - immunology; Toll-like receptors
• ISSN: 0973-1482; 1998-4138
• DOI: 10.4103/0973-1482.126460

Toll like receptors play an important role in innate and adaptive immune responses. Heat shock proteins play a significant role in cell proliferation, differentiation and oncogenesis. HSP70 acts as one of the ligands of TLR4 and binds to it in a CD14 dependent fashion to bring about proinflammatory cytokine production leading to an anti-tumor response. On the contrary, TLR4 has been implicated in carcinogenesis by secretion of anti-apoptotic proteins. Thus the aim of this study was to compare and correlate the association of HSP70 and TLR4 in various grades of oral squamous cell carcinoma. Twenty-seven cases of oral squamous cell carcinoma were considered. Ten cases each of well-differentiated (WDSCC) and moderately differentiated (MDSCC), 7 cases of poorly differentiated carcinoma (PDSCC) were considered. Sections were stained for HSP70 and TLR4 and were evaluated for staining degree and intensity. Positive expression of both HSP70 and TLR4 was found in all cases of WDSCC and MDSCC, whereas in PDSCC out of 7 cases only 6 showed positivity for TLR4 and 4 cases showed positivity for HSP70. Those cases that were positive for TLR4, also showed positivity for HSP70. HSP70 acts as a ligand and binds to TLR4 thus activating the My88 pathway resulting in production of proinflammatory cytokines, chemokines, growth factors etc., enhancing anti-cancer immunity in the early stages of disease. In later stages, TLRs expressed on cancer cells can produce anti-apoptotic proteins contributing to carcinogenesis and cancer cell proliferation.