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Article

Evolved Resistance to Placental Invasion Secondarily Confers Increased Survival in Melanoma Patients

by 1,2,3, 4 and 1,2,3,*
1
Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA
2
Cancer Systems Biology ([email protected]), Yale West Campus, West Haven, CT 06477, USA
3
Center for Cell Analysis and Modeling, University of Connecticut Health, Farmington, CT 06032, USA
4
Department of Cardiology, University of California, San Francisco, CA 94143, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Mohit Kumar Jolly
J. Clin. Med. 2021, 10(4), 595; https://doi.org/10.3390/jcm10040595
Received: 30 November 2020 / Revised: 29 January 2021 / Accepted: 2 February 2021 / Published: 5 February 2021
Mammals exhibit large differences in rates of cancer malignancy, even though the tumor formation rates may be similar. In placental mammals, rates of malignancy correlate with the extent of placental invasion. Our Evolved Levels of Invasibility (ELI) framework links these two phenomena identifying genes that potentially confer resistance in stromal fibroblasts to limit invasion, from trophoblasts in the endometrium, and from disseminating melanoma in the skin. Herein, using patient data from The Cancer Genome Atlas (TCGA), we report that these anti-invasive genes may be crucial in melanoma progression in human patients, and that their loss is correlated with increased cancer spread and lowered survival. Our results suggest that, surprisingly, these anti-invasive genes, which have lower expression in humans compared to species with non-invasive placentation, may potentially prevent stromal invasion, while a further reduction in their levels increases the malignancy and lethality of melanoma. Our work links evolution, comparative biology, and cancer progression across tissues, indicating new avenues for using evolutionary medicine to prognosticate and treat human cancers. View Full-Text
Keywords: melanoma metastasis; stromal invasion; cancer dissemination; cancer associated fibroblasts; invasibility; placentation; cancer microenvironment melanoma metastasis; stromal invasion; cancer dissemination; cancer associated fibroblasts; invasibility; placentation; cancer microenvironment
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MDPI and ACS Style

Suhail, Y.; Afzal, J.; Kshitiz. Evolved Resistance to Placental Invasion Secondarily Confers Increased Survival in Melanoma Patients. J. Clin. Med. 2021, 10, 595. https://doi.org/10.3390/jcm10040595

AMA Style

Suhail Y, Afzal J, Kshitiz. Evolved Resistance to Placental Invasion Secondarily Confers Increased Survival in Melanoma Patients. Journal of Clinical Medicine. 2021; 10(4):595. https://doi.org/10.3390/jcm10040595

Chicago/Turabian Style

Suhail, Yasir, Junaid Afzal, and Kshitiz. 2021. "Evolved Resistance to Placental Invasion Secondarily Confers Increased Survival in Melanoma Patients" Journal of Clinical Medicine 10, no. 4: 595. https://doi.org/10.3390/jcm10040595

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