Oral squamous cell carcinoma (OSCC) is a leading cause of mortality in India owing to the high percentage of tobacco chewers, smokers and alcohol consumption. OSCC is highly heterogeneous in nature; therefore poses a challenge in the treatment of the patient. To better understand the heterogeneity of the tumors, an in vitro cell line model is required. However, the efficiency of establishing cell lines from the oral tumors is low. In the present study, three novel cell lines, namely ACOSC3, ACOSC4, and ACOSC16, were isolated and characterized from advanced-stage treatment-naive OSCCs originating from the buccal mucosa. The three cell lines exhibited polygonal morphology, which is typical of epithelial cells. Furthermore, immunofluorescence revealed the expression of keratins 8 and 14, thereby confirming the epithelial origin of the cells. DNA content analysis of the three OSCC cell lines revealed aneuploidy. Furthermore, an in vitro orosphere assay revealed the formation of primary orospheres. Notably, the OSCC cell lines were able to give rise to tumors when administered subcutaneously into non-obese diabetic/severe combined immune deficiency mice. The novelty of the cell lines was also validated by performing short tandem repeat profiling; the STR profiles of the present cell lines did not significantly match with any known established OSCC cell lines present in the DSMZ database, thereby confirming the unique identity of these lines. These cell lines established from tumor samples derived from Indian OSCC patients provide a valuable resource to understand the molecular mechanism involved in tumor resistance and recurrence.

Secretory phospholipase A2 Group-IIA (sPLA2-IIA) is involved in lipid catabolism and growth promoting activity. sPLA2-IIA is deregulated in many pathological conditions including various cancers. Here, we have studied the role of sPLA2-IIA in the development of cyclic alopecia and wound healing response in relation to complete loss of hair follicle stem cells (HFSCs). Our data showed that overexpression of sPLA2-IIA in homozygous mice results in hyperproliferation and terminal epidermal differentiation followed by hair follicle cycle being halted at anagen like stage. In addition, sPLA2-IIA induced hyperproliferation leads to compl pathological conditions including various cancers. Here ete exhaustion of hair follicle stem cell pool at PD28 (Postnatal day). Importantly, sPLA2-IIA overexpression affects the hair shaft differentiation leading to development of cyclic alopecia. Molecular investigation study showed aberrant expression of Sox21, Msx2 and signalling modulators necessary for proper differentiation of inner root sheath (IRS) and hair shaft formation. Further, full-thickness skin wounding on dorsal skin of K14-sPLA2-IIA homozygous mice displayed impaired initial healing response. Our results showed the involvement of sPLA2-IIA in regulation of matrix cells differentiation, hair shaft formation and complete loss of HFSCs mediated impaired wound healing response. These novel functions of sPLA2-IIA may have clinical implications in alopecia, cancer development and ageing.

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