Environmental control of mammary carcinoma cell expansion by acidification and spheroid formation in vitro

Ana Carolina Lima Ralph, Iuri Cordeiro Valadão, Elaine Cristina Cardoso, Vilma Regina Martins, Luanda Mara Silva Oliveira, Estela Maris Andrade Forell Bevilacqua, Murilo Vieira Geraldo, Ruy Gastaldoni Jaeger, Gary S. Goldberg, Vanessa Morais Freitas

Research output: Contribution to journalArticlepeer-review

Abstract

Breast cancer is the leading cause of cancer death among women worldwide. Like other cancers, mammary carcinoma progression involves acidification of the tumor microenvironment, which is an important factor for cancer detection and treatment strategies. However, the effects of acidity on mammary carcinoma cell morphology and phenotype have not been thoroughly characterized. Here, we evaluated fundamental effects of environmental acidification on mammary carcinoma cells in standard two-dimensional cultures and three-dimensional spheroids. Acidification decreased overall mammary carcinoma cell viability, while increasing their resistance to the anthracycline doxorubicin. Environmental acidification also increased extracellular vesicle production by mammary carcinoma cells. Conditioned media containing these vesicles appeared to increase fibroblast motility. Acidification also increased mammary carcinoma cell motility when cultured with fibroblasts in spheroids. Taken together, results from this study suggest that environmental acidification induces drug resistance and extracellular vesicle production by mammary carcinoma cells that promote tumor expansion.

Original languageEnglish (US)
Article number21959
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - Dec 2020

All Science Journal Classification (ASJC) codes

  • General

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