Novel cancer associated fibroblasts from diverse locales enhance the tumorigenicity of tongue tumor epithelia

Author(s): Nehanjali Dwivedi, Hafsa Bahaar, DN Shashank, Christine Elizabeth Cherry, Charitha Gangadharan, Amritha Suresh, Moni A Kuriakose, Vijay Pillai, Smitha PK, and Manjula Das

Due to high rates of tobacco chewers, smokers, and alcohol consumers in India, Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the primary causes of mortality. Being profoundly varied in nature, treating patients diagnosed with HNSCC can be difficult. An invitro cell line model is needed to better comprehend the heterogeneity especially via the interaction with components of the microenvironment like Cancer Associated Fibroblasts (CAFs). The effectiveness of creating cell lines from head and neck cancers is, however, poor. Furthermore, except for the two reported earlier by the authors, no other immortalized CAF cell lines are available to study the cross-talk of the tumor with its microenvironment. In this study, the authors report three novel CAF lines, spontaneously immortalized, from Human Papilloma Virus (HPV) negative male patients with habits of tobacco and diagnosed with squamous cell carcinoma of the upper alveolus, larynx and buccal mucosa. Negative staining with EpCAM, CD31 and CD45, while positive staining with FSP-1 determined their fibroblast specific lineage. Interestingly, in indirect co-culture experiments all three CAFs, though isolated from tumors of different regions of the oral cavity, could increase the tumorigenicity of the epithelial cells from tongue-tumor indicating at a common “CAF-factor”. The developed CAF cell lines are the first of their kind from the mentioned sites, and can act as invaluable tools for learning the site-independent common language between tumor-stroma and tumor in HNSCC.