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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activated fibroblasts are thought to play important roles in the progression of many solid tumors, but little is known about the mechanisms responsible for the recruitment of fibroblasts in tumors. Using several methods, we identified platelet-derived growth factor A (PDGFA) as the major fibroblast chemoattractant and mitogen from conditioned medium generated by the Calu-6 lung carcinoma cell line. In addition, we showed that Calu-6 tumors express significant levels of PDGFC, and that the levels of expression of these two PDGFRalpha ligands correlate strongly with the degree of stromal fibroblast infiltration into the tumor mass. The most intense expression of PDGFRalpha was observed in fibroblasts in the tumor outer rim. We subsequently showed that disrupting PDGFRalpha-mediated signaling results in significant inhibition of tumor growth in vivo. Furthermore, analysis of a compendium of microarray data revealed significant expression of PDGFA, PDGFC, and PDGFRalpha in human lung tumors. We propose that therapies targeting this stromal cell type may be effective in treating certain types of solid tumors.
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PMID:Tumor-driven paracrine platelet-derived growth factor receptor alpha signaling is a key determinant of stromal cell recruitment in a model of human lung carcinoma. 1667 59

Cancer results from the concerted performance of malignant cells and stromal cells. Cell types populating the microenvironment are enlisted by the tumor to secrete a host of growth-promoting cues, thus upholding tumor initiation and progression. Platelet-derived growth factors (PDGF) support the formation of a prominent tumor stromal compartment by as of yet unidentified molecular effectors. Whereas PDGF-CC induces fibroblast reactivity and fibrosis in a range of tissues, little is known about the function of PDGF-CC in shaping the tumor-stroma interplay. Herein, we present evidence for a paracrine signaling network involving PDGF-CC and PDGF receptor-alpha in malignant melanoma. Expression of PDGFC in a mouse model accelerated tumor growth through recruitment and activation of different subsets of cancer-associated fibroblasts. In seeking the molecular identity of the supporting factors provided by cancer-associated fibroblasts, we made use of antibody arrays and an in vivo coinjection model to identify osteopontin as the effector of the augmented tumor growth induced by PDGF-CC. In conclusion, we establish paracrine signaling by PDGF-CC as a potential drug target to reduce stromal support in malignant melanoma.
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PMID:Paracrine signaling by platelet-derived growth factor-CC promotes tumor growth by recruitment of cancer-associated fibroblasts. 1911 22

Feline mammary carcinoma (FMC) is similar to human breast cancer in the late age of onset, incidence, histopathologic features, biological behavior, and pattern of metastasis. Therefore, FMC has been proposed as a relevant model for aggressive human breast cancer. The goals of this study were to develop a nude mouse model of FMC tumor growth and metastasis and to measure the expression of genes responsible for lymphangiogenesis, angiogenesis, tumor progression, and lymph node metastasis in FMC tissues and cell lines. Two primary FMC tissues were injected subcutaneously, and 6 FMC cell lines were injected into 3 sites (subcutaneous, intratibial, and intracardiac) in nude mice. Tumors and metastases were monitored using bioluminescent imaging and characterized by gross necropsy, radiology, and histopathology. Molecular characterization of invasion and metastasis genes in FMC was conducted using quantitative real-time reverse transcription polymerase chain reaction in 6 primary FMC tissues, 2 subcutaneous FMC xenografts, and 6 FMC cell lines. The histologic appearance of the subcutaneous xenografts resembled the primary tumors. No metastasis was evident following subcutaneous injection of tumor tissues and cell lines, whereas lung, brain, liver, kidney, eye, and bone metastases were confirmed following intratibial and intracardiac injection of FMC cell lines. Finally, 15 genes were differentially expressed in the FMC tissues and cell lines. The highly expressed genes in all samples were PDGFA, PDGFB, PDGFC, FGF2, EGFR, ERBB2, ERBB3, VEGFD, VEGFR3, and MYOF. Three genes ( PDGFD, ANGPT2, and VEGFC) were confirmed to be of stromal origin. This investigation demonstrated the usefulness of nude mouse models of experimental FMC and identified molecular targets of FMC progression and metastasis.
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PMID:Feline Mammary Cancer. 2728 Oct 14