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.

中文翻译：

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描绘非黑素瘤皮肤癌的细胞行为和代谢。

非黑色素瘤皮肤癌-基底细胞癌（BCC）和鳞状细胞癌（SCC）-是全世界人类最常见的恶性肿瘤形式。这些癌的病因是多因素的。除了紫外线的有害作用外，肿瘤上皮细胞与支持性真皮成纤维细胞之间的串扰改变也有助于调节肿瘤细胞的行为，生长和存活。这些细胞类型之间的代谢协作使它们能够通过修饰细胞生物能和生物合成来适应周围微环境的变化并对其做出反应。我们表征了在存在或不存在皮肤成纤维细胞的情况下，人BCC细胞，具有E-钙粘蛋白功能的SCC细胞和受E-钙粘蛋白抑制的SCC细胞的生长，行为和代谢活性。在单一文化和共文化中，BCC和SCC细胞表现出独特的形态，生长和组织模式。这些肿瘤细胞还表现出葡萄糖，乳酸盐，乙酸盐，谷氨酰胺，谷氨酸和丙酮酸的消耗和分泌曲线的独特模式。与单培养相比，BCC细胞或SCC细胞成纤维细胞的生长丰富了细胞生长环境，允许这两种细胞类型之间进行代谢协同作用，并导致了共培养的代谢谱改变。这些改变受癌细胞类型，培养融合度和生长培养基组成的影响。在肿瘤-基质相互作用的背景下表征BCC和SCC细胞的生物能学不仅对进一步了解肿瘤发病机理具有重要意义，而且可以阐明新型的潜在新靶点，