• John C Greenwell, Edilson Torres-Gonzalez, Jeffrey D Ritzenthaler, and Jesse Roman.
• Department of Pharmacology & Toxicology, University of Louisville Health Sciences Center, Louisville, KY, United States.
• Am. J. Med. Sci. 2023 Feb 1; 365 (2): 189197189-197.

AbstractLung cancer is the leading cause of cancer death in men and women in the United States. Recent studies have implicated the tumor microenvironment as a new chemotherapeutic target by demonstrating the importance of tumor cell-stromal interactions in cancer progression. However, the exact mechanisms by which tumor cell-stromal interactions drive lung cancer progression remain undefined, particularly in the lung. We suspect host fibroblasts represent an important component of the tumor microenvironment that drives tumor progression. We found that human non-small cell lung carcinoma cell lines show alterations in cell morphology, proliferation, migration, and colony formation on soft agar when exposed to fibroblast-conditioned media (FCM). Interestingly, FCM also promoted tumor cell resistance to cisplatin-induced apoptosis. These effects varied depending on the cancer cell line used. Similar observations were made when exposing murine Lewis Lung Carcinoma cells to conditioned media harvested from primary murine lung fibroblasts. Certain effects of FCM, but not all, could be prevented by using a cMET inhibitor. In vivo, we observed enhanced growth of the primary tumors when treated with FCM, but no changes in metastatic behavior. Although the identity of the stimulating agent(s) in the fibroblast-conditioned media was not unveiled, further studies revealed that the activity is more than one factor with a high-molecular weight (over 100 kDa). These studies implicate lung fibroblast-derived factors in lung cancer progression. These data suggest that targeting the lung tumor stroma alone, or in combination with other interventions, is a promising concept that warrants further study in the setting of lung cancer.Copyright © 2022. Published by Elsevier Inc.

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