Transforming growth factor-beta2 is a molecular determinant for site-specific melanoma metastasis in the brain.

Murine melanomas produce site-specific experimental brain metastases that reflect clinical reality. When injected into the internal carotid artery of mice, K-1735 melanoma cells produce metastatic lesions only in the brain parenchyma, whereas B16 melanoma cells and the somatic hybrid cells of B16 x K-1735 melanoma cells produce metastatic lesions only in the leptomeninges and ventricles. In the present study, we identified transforming growth factor-beta2 (TGF-beta2), an isoform of the TGF-beta family, as a molecular determinant of melanoma cell growth in the brain parenchyma.

Modification of the primary tumor microenvironment by transforming growth factor alpha-epidermal growth factor receptor signaling promotes metastasis in an orthotopic colon cancer model.

The transforming growth factor alpha (TGFalpha)/epidermal growth factor receptor (EGFR) signaling pathway appears to play a critical role in colon cancer progression, but the cellular and molecular mechanisms that contribute to metastasis remain unknown. KM12C colon cancer cell clones expressing high (C9) or negligible (C10) levels of TGFalpha were implanted into the cecal walls of nude mice. C9 tumors formed autocrine and paracrine EGFR networks, whereas C10 tumors were unable to signal through EGFR.

Survival of cancer cells is maintained by EGFR independent of its kinase activity.

Expression of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase associated with cell proliferation and survival, is overactive in many tumors of epithelial origin. Blockade of the kinase activity of EGFR has been used for cancer therapy; however, by itself, it does not seem to reach maximum therapeutic efficacy. We report here that in human cancer cells, the function of kinase-independent EGFR is to prevent autophagic cell death by maintaining intracellular glucose level through interaction and stabilization of the sodium/glucose cotransporter 1 (SGLT1).

Inhibition of epidermal growth factor receptor and vascular endothelial growth factor receptor phosphorylation on tumor-associated endothelial cells leads to treatment of orthotopic human colon cancer in nude mice.

The purpose of our study was to determine whether the dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways in tumor-associated endothelial cells can inhibit the progressive growth of human colon carcinoma in the cecum of nude mice. SW620CE2 human colon cancer cells growing in culture and orthotopically in the cecum of nude mice expressed a high level of transforming growth factor alpha (TGF-alpha) and vascular endothelial growth factor (VEGF) but were negative for EGFR, human epidermal growth factor receptor 2 (HER2), and VEGFR. Double immunofluorescence staining revealed that tumor-associated endothelial cells expressed EGFR, VEGFR2, phosphorylated EGFR (pEGFR), and phosphorylated VEGFR (pVEGFR).

Expression of epidermal growth factor (EGF)/transforming growth factor-alpha by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice.

Epidermal growth factor receptor (EGFR) has been extensively targeted in the treatment of non-small cell lung cancer, producing responses in a small number of patients. To study the role of ligand expression in mediating response to EGFR antagonism, we injected NCI-H441 [EGFR and EGF/transforming growth factor-alpha (TGF-alpha) positive] or PC14-PE6 (EGFR positive and EGF/TGF-alpha negative) human lung adenocarcinoma cells into the lungs of nude mice. We randomized the mice to receive treatment with the EGFR tyrosine kinase inhibitors gefitinib or AEE788 or vehicle.