Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression.

Arteaga, Carlos L.; Hurd, Stephen D.; Winnier, Angela R.; Johnson, M. D.; Fendly, Brian M.; Forbes, James T.

doi:10.1172/jci116871

Cited by 324 publications

(195 citation statements)

References 32 publications

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“…Additionally, we validated COX2 and TGFB2 protein expression in vivo in CAFs of metastatic cancer in the liver. Both PIGS2 (COX2) and TGFB2 are thought to have an important role in the cancer microenvironment (Arteaga et al, 1993;Oshima et al, 1996;Williams et al, 2000;Derynck et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles

et al. 2004

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The cancer microenvironment and interaction between cancer and stromal cells play critical roles in tumor development and progression. The molecular features of cancer stroma are less well understood than those of cancer cells. Cancer-associated stromal fibroblasts are the predominant component of stroma associated with colon cancer and its functions remain unclear. Fibroblast cell cultures were established from metastatic colon cancer in liver, liver away from the metastatic lesions, and skin from three patients with metastatic colorectal cancer. We generated expression profiles of cancer-associated fibroblasts using oligochip arrays and compared them to those of uninvolved fibroblasts. The conditioned media from the cancer-associated fibroblast cultures enhanced proliferation of colon cancer cell line HCT116 to a greater extent than cultures from uninvolved fibroblasts. In microarray expression analysis, cancer-associated fibroblasts clustered tightly into one group and skin fibroblasts into another. Approximately 170 of 22 000 genes were upregulated in cancer-associated fibroblasts (fold change42, Po0.05) as compared to skin fibroblasts, including many genes encoding cell adhesion molecules, growth factors, and COX2. By immunohistochemistry in-vivo, we confirmed COX2 and TGFB2 expression in cancer-associated fibroblasts in metastatic colon cancer. The distinct molecular expression profiles of cancerassociated fibroblasts in colon cancer metastasis support the notion that these fibroblasts form a favorable microenvironment for cancer cells.

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Section: Discussionmentioning

confidence: 99%

Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles

et al. 2004

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“…A highly immunogenic tumour transfected with a murine TGF-j1 cDNA escaped immune surveillance in mice, and TGF-[2 has been identified as the T-cell suppressor factor of human glioblastoma (de Martin et al, 1987;Torre-Amione et al, 1990). Furthermore, treatment of mice with anti-TGF-[B antibodies inhibited growth of human breast cancer cells by enhancing spleen NK-cell activity (Arteaga et al, 1993). In addition, B16 melanoma growth and metastasis in vivo was inhibited by treatment of mice with anti-transforming growth factor beta antibody and interleukin 2 (Wojtowicz-Praga et al, 1996), indicating that therapeutic interventions for blocking systemic TGF-[B overexpression should be taken under further consideration.…”

Section: Discussionmentioning

confidence: 99%

Elevated plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 in patients with disseminated malignant melanoma

Krasagakis

Thölke²,

Farthmann³

et al. 1998

Br J Cancer

136

101

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Summary Overexpression of transforming growth factor-4 isoforms (TGF-f1, -P2, -,B3) has been previously reported in human melanoma cell lines and tumours. The aim of the present study was to evaluate the plasma levels of TGF-f isoforms in melanoma patients. Significantly elevated levels of TGF-,1l (4.2 x the controls, P= 0.0094) and of TGF-,2 (1.5 x the controls, P= 0.012) but not of TGF-13 were measured in patients with disseminated but not locoregional melanoma. These results indicate systemic circulation of potentially immunosuppressive peptides of the TGF-P family in end-stage melanoma patients.

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“…This activation process, however, is blocked by TGFb [65]. Additional targets of TGFb-mediated immune evasion include natural killer cells and neutrophils [66][67][68]. Collectively, evidence from both xenograft and transgenic models demonstrates a critical role for TGFb in enabling cancer progression through the suppression of the host immune system.…”

Section: Immune Suppression/evasionmentioning

confidence: 99%

Roles of TGFβ in metastasis

2008

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The TGFβ signaling pathway is conserved from flies to humans and has been shown to regulate such diverse processes as cell proliferation, differentiation, motility, adhesion, organization, and programmed cell death. Both in vitro and in vivo experiments suggest that TGFβ can utilize these varied programs to promote cancer metastasis through its effects on the tumor microenvironment, enhanced invasive properties, and inhibition of immune cell function. Recent clinical evidence demonstrating a link between TGFβ signaling and cancer progression is fostering interest in this signaling pathway as a therapeutic target. Anti-TGFβ therapies are currently being developed and tested in preclinical studies. However, targeting TGFβ carries a substantial risk as this pathway is implicated in multiple homeostatic processes and is also known to have tumor-suppressor functions. Additionally, clinical and experimental results show that TGFβ has diverse and often conflicting roles in tumor progression even within the same tumor types. The development of TGFβ inhibitors for clinical use will require a deeper understanding of TGFβ signaling, its consequences, and the contexts in which it acts.

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Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression.

Cited by 324 publications

References 32 publications

Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles

Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles

Elevated plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 in patients with disseminated malignant melanoma

Roles of TGFβ in metastasis

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