Breast Cancer: Induction of Differentiation by Embryonic Tissue

DeCosse, Jerome J.; Gossens, Carol Lynn; Kuzma, Joseph F.; Unsworth, Brian R.

doi:10.1126/science.181.4104.1057

Cited by 119 publications

(52 citation statements)

References 8 publications

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“…These studies have revealed that fibroblasts can both inhibit and enhance tumor growth. The cocultivation of fibroblasts with mammary carcinoma cells exhibits a more orderly histological differentiation (62,63) and basal cell carcinoma cells grown in association with stromal cells demonstrated a loss of their malignant properties (64). In contrast, other studies revealed that TAF have a growth-stimulating effect upon tumors in vitro (65)(66)(67) and in vivo (68 -70).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Human Lung Tumor-Associated Fibroblasts and Their Ability to Modulate the Activation of Tumor-Associated T Cells

Nazareth

Broderick

Simpson-Abelson

et al. 2007

The Journal of Immunology

231

191

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The tumor microenvironment of human non-small cell lung cancer (NSCLC) is composed largely of stromal cells, including fibroblasts, yet these cells have been the focus of few studies. In this study, we established stromal cell cultures from primary NSCLC through isolation of adherent cells. Characterization of these cells by flow cytometry demonstrated a population which expressed a human fibroblast-specific 112-kDa surface molecule, Thy1, α-smooth muscle actin, and fibroblast activation protein, but failed to express CD45 and CD11b, a phenotype consistent with that of an activated myofibroblast. A subset of the tumor-associated fibroblasts (TAF) was found to express B7H1 (PD-L1) and B7DC (PD-L2) constitutively, and this expression was up-regulated by IFN-γ. Production of cytokines and chemokines, including IFN-γ, monokine induced by IFN-γ, IFN-γ-inducible protein-10, RANTES, and TGF-β1 was also demonstrated in these cells. Together, these characteristics provide multiple opportunities for the TAF to influence cellular interactions within the tumor microenvironment. To evaluate the ability of TAF to modulate tumor-associated T cell (TAT) activation, we conducted coculture experiments between autologous TAF and TAT. In five of eight tumors, TAF elicited a contact-dependent enhancement of TAT activation, even in the presence of a TGF-β1-mediated suppressive effect. In the three other tumors, TAF had a net suppressive effect upon TAT activation, and, in one of these cases, blockade of B7H1 or B7DC was able to completely abrogate the TAF-mediated suppression. We conclude that TAF in human NSCLC are functionally and phenotypically heterogeneous and provide multiple complex regulatory signals that have the potential to enhance or suppress TAT function in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Characterization of Human Lung Tumor-Associated Fibroblasts and Their Ability to Modulate the Activation of Tumor-Associated T Cells

Nazareth

Broderick

Simpson-Abelson

et al. 2007

The Journal of Immunology

231

191

View full text Add to dashboard Cite

show abstract

“…[28][29][30][31][32][33] Breast carcinoma cells exhibit a reduction in proliferation when cultured in the presence of normal breast mesenchymal cells. 26 In addition to effects on proliferation, normal stroma can also induce the differentiation of transformed cells. Work demonstrated that intestinal epithelial cell lines derived from colonic adenocarcinomas exhibit normal morphology and functional differentiation when cocultured with embryonic rat mesenchyme.…”

Section: The Role Of Stroma As a Tumor Suppressormentioning

confidence: 99%

Stroma: Tumor Agonist or Antagonist

Proia

Kuperwasser²

2005

Cell Cycle

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“…However it is also important to note that the normal mammary gland microenvironment has inhibitory effect on breast cancer progression (DeCosse et al, 1973). This indicates that cancer cells can maintain their properties only in an abnormal microenvironment.…”

Section: Microenvironment Of Breast Cancer Cellsmentioning

confidence: 99%