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

Author(s)

Lima Ralph, Ana Carolina ^[1] ; Valadao, Iuri Cordeiro ^[1] ; Cardoso, Elaine Cristina ^[1] ; Martins, Vilma Regina ^[2] ; Silva Oliveira, Luanda Mara ^[3] ; Andrade Forell Bevilacqua, Estela Maris ^[1] ; Geraldo, Murilo Vieira ^[4] ; Jaeger, Ruy Gastaldoni ^[1] ; Goldberg, Gary S. ^{[5, 6]} ; Freitas, Vanessa Morais ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil

^[2] Natl Inst Sci & Technol Oncogen & Therapeut Innov, AC Camargo Canc Ctr, Inte Res Ctr, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Med Sch, Lab Dermatol & Immunodeficiencies LIM 56, Dept Dermatol, Inst Trop Med, Sao Paulo - Brazil

^[4] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas - Brazil

^[5] Rowan Univ, Sch Osteopath Med, Grad Sch Biomed Sci, Stratford, NJ - USA

^[6] Rowan Univ, Sch Osteopath Med, Dept Mol Biol, Stratford, NJ - USA

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 DEC 15 2020.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 19/00496-2 - Cell communication in cancer: role of proteases and extracellular vesicles on tumor microenvironment
• Grantee: Vanessa Morais Freitas
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• FAPESP's process: 15/02498-1 - Biological significance of stress on the modulation of the tumor-stemness phenotype
• Grantee: Vanessa Morais Freitas
• Support Opportunities: Regular Research Grants