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Delineating cell behavior and metabolism of non-melanoma skin cancer in vitro

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Abstract

Non-melanoma skin cancers - basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) - are the most frequent forms of malignant neoplasm in humans worldwide. The etiology of these carcinomas is multifactorial. In addition to the harmful effect of UV light, altered cross-talk between neoplastic epithelial cells and the supporting dermal fibroblasts contributes to the regulation of tumor cell behavior, growth and survival. Metabolic cooperation between these cell types allows them to adapt and react to changes in their surrounding microenvironment by modifying their cellular bioenergetics and biosynthesis. We characterized the growth, behavior, and metabolic activity of human BCC cells, E-cadherin-competent SCC cells and E-cadherin-suppressed SCC cells in the presence or absence of dermal fibroblasts. In mono-cultures and co-cultures, BCC and SCC cells demonstrated distinct morphology, growth and organizational patterns. These tumor cells also exhibited unique patterns of consumption and secretion profiles of glucose, lactate, acetate, glutamine, glutamate, and pyruvate. In comparison to mono-cultures, growth of fibroblasts with either BCC cells or SCC cells enriched the cell growth environment, allowed for metabolic cooperation between these two cell types, and resulted in alterations in the metabolic profiles of the co-cultures. These alterations were affected by the cancer cell type, culture confluence and the composition of the growth medium. Characterizing the bioenergetics of BCC and SCC cells in the context of tumor-stromal interactions is not only important for further understanding of tumor pathogenesis, but also can illuminate potential new targets for novel, metabolic-based therapies for non-melanoma skin cancers.

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Acknowledgments

This research was supported by research grants from the Michael J. Rainen Family foundation (to A.A-H.). The work utilized NMR instrumentation that was purchased with funding from a National Institutes of Health SIG grant (S10OD020073). The authors wish to express their gratitude to Dr. Sarah Pagni and Tamar Roomian from the Division of Biostatistics and Experimental Design at Tufts University School of Dental Medicine, for the statistical analysis of the results. We thank Dr. J.A. Garlick (Tufts University School of Dental Medicine) for the gift of E-cadherin-competent and E-cadherin-suppressed SCC cells. We would also like to thank S. Kamlarz and Drs. J. Nolan and R. Tay for their technical assistance, and S. Kasraie for critical comments. We wish to express our heartfelt appreciation to Kristi Schmitt Burr, the Founder and former Executive Director of the BCC Nevus Syndrome Life Support Network, who inspired this study.

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Authors and Affiliations

  1. Department of Endodontics, Tufts University School of Dental Medicine, One Kneeland St, Boston, MA, 02111, USA

    Tatiana Mendez & Addy Alt-Holland

  2. Tufts University School of Dental Medicine, One Kneeland St, Boston, MA, 02111, USA

    Shawheen Saffari & Addy Alt-Holland

  3. Department of Pathology and Laboratory Medicine, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA

    Janet M. Cowan

  4. Department of Oral and Maxillofacial Pathology, Tufts University School of Dental Medicine, One Kneeland St, Boston, MA, 02111, USA

    Nora M. V. Laver

  5. Department of Ophthalmology and Pathology, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA

    Nora M. V. Laver

  6. Department of Medical Education and Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 136 Harrison Ave, Boston, MA, 02111, USA

    James D. Baleja

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  1. Tatiana Mendez
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  2. Shawheen Saffari
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Correspondence to Addy Alt-Holland.

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This study and experimental protocols were approved by the Institutional Review Board of Tufts University.

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Editor: Tetsuji Okamoto

Tatiana Mendez and Shawheen Saffari are co-first authors

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Mendez, T., Saffari, S., Cowan, J.M. et al. Delineating cell behavior and metabolism of non-melanoma skin cancer in vitro. In Vitro Cell.Dev.Biol.-Animal 56, 165–180 (2020). https://doi.org/10.1007/s11626-019-00416-6

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