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

AbstractBreast 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.

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Dexamethasone modulation of in vitro growth pattern and of lung colonization ability in clones of a metastatic BALB/c mammary carcinoma cell line

Clinical & Experimental Metastasis ◽

10.1007/bf00053469 ◽

1986 ◽

Vol 4 (1) ◽

pp. 13-23 ◽

Cited By ~ 2

Author(s):

Carla De Giovanni ◽

Pier-Luigi Lollini ◽

Giordano Nicoletti ◽

Sandro Grilli ◽

Giorgio Prodi ◽

...

Keyword(s):

Cell Line ◽

Mammary Carcinoma ◽

Growth Pattern ◽

Carcinoma Cell ◽

In Vitro Growth ◽

Mammary Carcinoma Cell ◽

Mammary Carcinoma Cell Line ◽

Lung Colonization ◽

Colonization Ability

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Signal Transducer and Activator of Transcription (STAT)-5A and STAT5B Differentially Regulate Human Mammary Carcinoma Cell Behavior

Endocrinology ◽

10.1210/en.2009-0651 ◽

2010 ◽

Vol 151 (1) ◽

pp. 43-55 ◽

Cited By ~ 37

Author(s):

Jian-Zhong Tang ◽

Ze-Hua Zuo ◽

Xiang-Jun Kong ◽

Michael Steiner ◽

Zhinan Yin ◽

...

Keyword(s):

Cell Motility ◽

Mammary Carcinoma ◽

Carcinoma Cell ◽

Carcinoma Cells ◽

Signal Transducer ◽

Human Mammary Carcinoma ◽

Anchorage Independent Growth ◽

Human Mammary Carcinoma Cell ◽

Mammary Carcinoma Cells ◽

Interfering Rna

Abstract Increased activation of signal transducer and activator of transcription (STAT)-5 has been reported in various malignancies including mammary carcinoma. However, it is only recently that potentially distinct roles of STAT5A and STAT5B in neoplasia have begun to emerge. Herein we systematically delineate the functions of STAT5A and STAT5B in human mammary carcinoma cell lines MCF-7 and T47D. Forced expression of constitutively active (CA) STAT5A enhanced both survival and anchorage-independent growth of human mammary carcinoma cells but concordantly suppressed cell motility as revealed in colony scattering, cell migration, and invasion assays. In contrast, forced expression of CA STAT5B exhibited lower potency than CA STAT5A in enhancing survival and anchorage-independent growth of mammary carcinoma cells and exerted no effects on cell motility. Differential expression of genes that regulate cellular survival and motility was concomitantly observed on forced expression of CA STAT5A or CA STAT5B. Small interfering RNA-mediated depletion of STAT5A significantly impaired anchorage-independent growth of human mammary carcinoma cells, whereas a smaller reduction was observed upon small interfering RNA-mediated depletion of STAT5B. Depletion of endogenous STAT5A also significantly enhanced cell motility, whereas depletion of endogenous STAT5B exhibited no effect. Xenograft studies provided data concordant with the in vitro effects of the two STAT5 isoforms. We therefore demonstrate that STAT5A and STAT5B differentially regulate behavior of human mammary carcinoma cells.

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