Mammary fibroblasts stimulate growth, alveolar morphogenesis, and functional differentiation of normal rat mammary epithelial cells

Darcy, Kathleen M.; Zangani, Danilo; Shea-Eaton, Wendy; Shoemaker, Suzanne F.; Lee, Ping-Ping H.; Mead, Lawrence H.; Mudipalli, Anuradha; Megan, Roberta; Ip, Margot M.

doi:10.1007/bf02577526

Cited by 31 publications

(18 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14,[16][17][18][21][22][23][24] We recently demonstrated that a significant proportion of myofibroblasts was recruited from the BM and had proliferative activity in the subcutaneously transplanted tumors of a human pancreatic cancer cell line, Capan-1. 13 In our study, we clearly demonstrated that 7 other human cancer cell lines also recruited BMD-VE and/or -MF into the cancer stroma in the subcutaneous tissue and induced neovascularization and myofibroblast proliferation to a greater or less extent.…”

Section: Discussionmentioning

confidence: 99%

Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow‐derived endothelial cells and myofibroblasts in cancer‐induced stroma

Sangai¹,

Ishii²,

Kodama³

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Cancer-stromal interaction is well known to play important roles during cancer progression. Recently we have demonstrated that bone marrow-derived vascular endothelial cells (BMD-VE) and myofibroblasts (BMD-MF) are recruited into the human pancreatic cancer cell line Capan-1 induced stroma. To assess the effect of the difference in cancer cell types on the recruitment of BMD-VE and BMD-MF, 10 kinds of human cancer cell line were implanted into the subctaneous tissue of the immunodeficient mice transplanted with bone marrow of double-mutant mice (RAG-12/2 b-gal Tg or RAG-12/2 GFP Tg). The recruitment frequency of BMD-VE (%BMD-VE) and BMD-MF (%BMD-MF), and tumor-associated parameters [tumor volume (TV), microvessel density (MVD) and stromal proportion (%St)] were measured. The correlation among them was analyzed. Although %BMD-VE and %BMD-MF varied (from 0 to 21.6%, 0 to 29.6%, respectively), depending on the cancer cell line, both parameters were significantly correlated with %St (p < 0.005). Furthermore %BMD-VE and %BMD-MF also significantly correlated (p < 0.005). In order to assess the effect of tumor growth sites on the recruitment of the cells of interest, a human pancreatic cancer cell line, Capan-1, was transplanted into 5 different sites: subcutaneous tissue, peritoneum, liver, spleen and lung. Tumors in the subcutaneous tissue and peritoneum induced desmoplastic stroma (%St ¼ 22.7%, 19.5%, respectively) and contained BMD-VE (%BMD-VE ¼ 21.6%, 16.5% respectively) and BMD-MF (%BMD-MF ¼ 29.6%, 24.5%, respectively), but weak stromal induction without recruitment of BMD-VE or -MF was observed in the tumors at of the liver, spleen and lung (%St ¼ 9.7%, 9.1%, 5.4%, respectively). cDNA microarray analysis identified the 29 genes that expression was especially upor down-regulated in the cell line that induced an abundant stromal reaction. However they did not encoded the molecules that were directly involved in stromal cell recruitment (chemokines), differentiation (cytokines) or proliferation (growth factors). These results indicate that the recruitment of BMD-VE and -MF is required for stromal formation during cancer progression and that the cancer microenvironment is important in stromal reaction and the recruitment of BMD-VE and -MF. ' 2005 Wiley-Liss, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow‐derived endothelial cells and myofibroblasts in cancer‐induced stroma

Sangai¹,

Ishii²,

Kodama³

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…This differentiation requires both hormonal and ECM-mediated signals (Rosen et al, 1999), as well as signals from surrounding stromal fibroblasts (Darcy et al, 2000).…”

Section: Senescent Fibroblasts Disrupt Morphological and Functional Dmentioning

confidence: 99%

Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation

Parrinello

Coppé

Krtolica

et al. 2005

Journal of Cell Science

548

423

View full text Add to dashboard Cite

Cellular senescence suppresses cancer by arresting cells at risk of malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation and branching morphogenesis. Furthermore, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts - the ability to alter epithelial differentiation - that might also explain the loss of tissue function and organization that is a hallmark of aging.

show abstract

“…Moreover, when cocultured with mammary adipocytes, primary rat MECs exhibit enhanced differentiation, as measured by lipid and casein accumulation (78). Similarly, coculture with mammary fibroblasts promotes MEC alveolar morphogenesis, proliferation and differentiation (79).…”

Section: Modeling Epithelial-stromal Interactionsmentioning

confidence: 99%

Use of Three-Dimensional Basement Membrane Cultures to Model Oncogene-Induced Changes in Mammary Epithelial Morphogenesis

Shaw

Wrobel

Brugge

2004

J Mammary Gland Biol Neoplasia

137

117

View full text Add to dashboard Cite

The development of breast carcinomas involves a complex set of phenotypic alterations in breast epithelial cells and the surrounding microenvironment. While traditional transformation assays provide models for investigating certain aspects of the cellular processes associated with tumor initiation and progression, they do not model alterations in tissue architecture that are critically involved in tumor development. In this review, we provide examples of how three-dimensional (3D) cell culture models can be utilized to dissect the pathways involved in the development of mammary epithelial structures and to elucidate the mechanisms responsible for oncogene-induced phenotypic alterations in epithelial behavior and architecture. Many normal mammary epithelial cell lines undergo a stereotypic morphogenetic process when grown in the presence of exogenous matrix proteins. This 3D morphogenesis culminates in the formation of well-organized, polarized spheroids, and/or tubules that are highly reminiscent of normal glandular architecture. In contrast, transformed cell lines isolated from mammary tumors exhibit significant deviations from normal epithelial behavior in 3D culture. We describe the use of 3D models as a method for both reconstructing and deconstructing the cell biological and biochemical events involved in mammary neoplasia.Keywords mammary epithelial cells; breast cancer; morphogenesis; 3D cell culture; oncogenesis Abbreviations used3D; three-dimensional; BARD-1, BRCA-1 associated ring domain; CDK, cyclin-dependent kinase; CGH, comparative genomic hybridization; CSF-1, colony-stimulating factor; CSF-1R, colonystimulating factor receptor; DCIS, ductal carcinoma in situ; E7, human papilloma virus 16 E7 protein; ECM, extracellular matrix; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; EHS, Engelbreth-Holm-Swarm; EMT, epithelial-to-mesenchymal transition; ER, estrogen receptor; GAP, GTPase activating protein; GEF, guanine nucleotide exchange factor; HGF, hepatocyte growth factor; IGF, insulin-like growth factor; IL-1, interleukin-1; MAPK, mitogen-activated protein kinase; MEC, mammary epithelial cell; MMP, matrix metalloproteinase; MMTV, mouse mammary tumor virus; PI3K, phosphotidylinositol-3 kinase; PR, progesterone receptor; Rb, retinoblastoma protein; TGFβ, transforming growth factor beta; VEGF, vascular endothelial growth factor 2 To whom correspondence should be addressed at Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115; e-mail: joan brugge@hms.harvard.edu.. 3 These authors contributed equally to this review. NIH Public AccessAuthor Manuscript J Mammary Gland Biol Neoplasia. Author manuscript; available in PMC 2006 July 17. FROM SOFT AGAR TO BASEMENT MEMBRANE GELS: MODELING MAMMARY TUMORIGENESIS IN VITROThe mammary gland is a complex organ, comprised of multiple cell types and surrounded by a proteinaceous extracellular matrix (ECM). Mammary epithelial cells (MECs) represent the fundamental functional unit of the gland and comprise a polariz...

show abstract

Mammary fibroblasts stimulate growth, alveolar morphogenesis, and functional differentiation of normal rat mammary epithelial cells

Cited by 31 publications

References 94 publications

Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow‐derived endothelial cells and myofibroblasts in cancer‐induced stroma

Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow‐derived endothelial cells and myofibroblasts in cancer‐induced stroma

Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation

Use of Three-Dimensional Basement Membrane Cultures to Model Oncogene-Induced Changes in Mammary Epithelial Morphogenesis

Contact Info

Product

Resources

About