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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the last years it became clear that the tumor microenvironment plays a major role in neoplastic growth. Proteins secreted either by the malignant cells or by the tumor-associated stromal cells act as extracellular signal transductors, orchestrating tumor progression. Sentinel cells of the innate immune system patrol the different organs and have proven either to promote tumor growth or induce tumor suppression. In recent years, members of the matricellular family of extracellular proteins were shown to be involved in different aspects of the inflammatory response during tumor development, although in contradictory ways. In this review we discuss the evidence available up to date that relates matricellular proteins with the regulation of the inflammatory response and tumor progression.
Cytokine Growth Factor Rev 2010 Feb
PMID:Matricellular proteins and inflammatory cells: a task force to promote or defeat cancer? 2000 33

The transforming growth factor beta (TGF-beta) has been studied with regard to the regulation of cell behavior for over three decades. A large body of research has been devoted to the regulation of epithelial cell and derivative carcinoma cell populations in vitro and in vivo. TGF-beta has been shown to inhibit epithelial cell cycle progression and promote apoptosis that together significantly contribute to the tumor suppressive role for TGF-beta during carcinoma initiation and progression. TGF-beta is also able to promote an epithelial to mesenchymal transition that has been associated with increased tumor cell motility, invasion and metastasis. However, it has now been shown that loss of carcinoma cell responsiveness to TGF-beta stimulation can also promote metastasis. Interestingly, enhanced metastasis in the absence of a carcinoma cell response to TGF-beta stimulation has been shown to involve increased chemokine production resulting in recruitment of pro-metastatic myeloid derived suppressor cell (MDSC) populations to the tumor microenvironment at the leading invasive edge. When present, MDSCs enhance angiogenesis, promote immune tolerance and provide matrix degrading enzymes that promote tumor progression and metastasis. Further, the recruitment of MDSC populations in this context likely enhances the classic role for TGF-beta in immune suppression since the MDSCs are an abundant source of TGF-beta production. Importantly, it is now clear that carcinoma-immune cell cross-talk initiated by TGF-beta signaling within the carcinoma cell is a significant determinant worth consideration when designing therapeutic strategies to manage tumor progression and metastasis.
Cytokine Growth Factor Rev 2010 Feb
PMID:Transforming growth factor beta (TGF-beta) and inflammation in cancer. 2001 51

Inflammation has long been thought to contribute to the development of cancer; however there is also clear evidence that the immune system can recognize and eliminate cancer cells. Current research suggests that cancer-associated inflammation has a dual role in tumor progression; inflammatory mediators promote the malignant activity of cancer cells by acting as growth factors and also stimulate angiogenesis, however, cancer-associated inflammation is also linked with immune-suppression that allows cancer cells to evade detection by the immune system. In this review we will discuss the dual role of inflammation in cancer and how endogenous anti-inflammatory mechanisms may equally be important in carcinogenesis.
Cytokine Growth Factor Rev 2010 Feb
PMID:The resolution of inflammation and cancer. 2002 97

Invasion and metastasis are key components of cancer progression. Inflammatory mediators, including cytokines and chemokines, can facilitate tumor dissemination. A distinct and largely forgotten path is perineural invasion (PNI), defined as the presence of cancer cells in the perinerium space. PNI is frequently used by many human carcinomas, in particular by pancreas and prostate cancer, and is associated with tumor recurrence and pain in advanced patients. Neurotrophic factors have been identified as molecular determinants of PNI. A role for chemokines in this process has been proposed; the chemokine CX3CL1/Fractalkine attracts receptor positive pancreatic tumor cells to disseminate along peripheral nerves. Better understanding of the neurotropism of malignant cells and of the clinical significance of PNI would help the design of innovative strategies for the control of tumor dissemination and pain in cancer patients.
Cytokine Growth Factor Rev 2010 Feb
PMID:Molecular mechanisms of perineural invasion, a forgotten pathway of dissemination and metastasis. 2006 Jul 68

Ets-1 is a transcription factor that is highly expressed within lymphoid cells, where it is known to control their differentiation, survival and proliferation. Ets-1 is also expressed in other cell types and can be further induced by a variety of stimuli. Accumulating evidence points to an important role for Ets-1 in regulating the differentiation of T helper cell subsets, cytotoxic T cells, B cells and other cell types. Ets-1 also directly controls the expression of cytokine and chemokine genes in a wide variety of different cellular contexts. In this review, we summarize the known roles for Ets-1 in regulating the differentiation of immune cells and other cell types. Furthermore, we review in detail the current understanding of Ets-1 regulation of cytokine and chemokine expression and how this may relate to the biological roles of Ets-1 in regulating immunity as well as in cancer progression.
Cytokine 2010 Sep
PMID:Transcription factor Ets-1 in cytokine and chemokine gene regulation. 2037 71

Bone morphogenetic proteins (BMPs) were first studied as growth factors or morphogens of the transforming growth factor-beta superfamily. These growth molecules, originally associated with bone and cartilage development, are now known to play an important role in morphogenesis and homeostasis in many other tissues. More recently, significant contributions from BMPs, their receptors, and interacting molecules have been linked to carcinogenesis and tumor progression. On the other hand, BMPs can sometimes function as a tumor suppressor. Our report highlights these new roles in the pathogenesis of cancer that may suggest novel targets for therapeutic intervention.
Cytokine Growth Factor Rev 2010 Aug
PMID:The Yin and Yang of bone morphogenetic proteins in cancer. 2068 57

Interferon-induced transmembrane (IFITM) genes are transcribed in most tissues and are with the exception of IFITM5 interferon inducible. They are involved in early development, cell adhesion, and control of cell growth. Most IFITM genes are activated in response to bacterial and viral infections, and the exact host immune defense mechanisms are still unknown. Elevated gene expression triggered by past or chronic inflammation could prevent spreading of pathogens by limiting host cell proliferation. Accordingly, induction in cells with low basal protein levels is sufficient to drive growth arrest and a senescence-like morphology. On the other hand, loss of IFITM levels in cancer is correlated with pronounced malignancy; thus, these genes are considered as tumor suppressors. However, several cancer cells have deregulated high levels of IFITM transcripts, indicating a tumor progression stage where at least one of the interferon-controlled antiproliferative pathways has been silenced. Phylogenetic analyses of the protein coding genomic sequences suggest a single interferon-inducible gene in the common ancestor of rodents and primates. Biological functions studied so far may have evolved in parallel, and functional characterization of IFITM proteins will provide insight into innate immune defense, cancer development, and other pathways.
J Interferon Cytokine Res 2011 Jan
PMID:The small interferon-induced transmembrane genes and proteins. 2116 91

The predominant role of matrix metalloproteinase 8 in extracellular matrix turnover, modulation of inflammatory responses and other physiological processes is well documented. Several recent studies highlight the involvement of MMP8 in a wide range of pathologies. This review will shed light on the putative role of MMP8 as a drug target or disease marker in some inflammatory disorders and in cancer progression.
Cytokine Growth Factor Rev 2011 Apr
PMID:Matrix metalloproteinase8 has a central role in inflammatory disorders and cancer progression. 2138 56

Vascular endothelial growth factor C (VEGF-C) is a key regulator of angiogenesis and lymphangiogenesis. VEGF-C is also implicated in the development of esophageal cancer. We investigated the mRNA levels of VEGF-C and its receptors in 38 esophageal squamous cell carcinoma specimens (ESCCs) and matched adjacent normal esophageal tissues via real-time PCR. The mRNA levels of VEGF-C, VEGFR-2 and VEGFR-3 were significantly upregulated in ESCCs versus respective side normal tissues. To explore the influence of VEGF-C on esophageal cancer progression, the expression of VEGF-C was manipulated in esophageal cancer cell lines TE-1 and Eca-109. VEGF-C transcription, translation and secretion were significantly enhanced in cells stably transfected with a VEGF-C overexpression vector or attenuated in VEGF-C shRNA-transfected cell lines. In vitro, TE-1 cells stably transfected with a VEGF-C overexpression vector exhibited an increased rate of cell proliferation, migration and focus formation, whereas knockdown of VEGF-C inhibited cell proliferation, migration and focus formation. Similar results were obtained for Eca-109 cells. VEGF-C mediated biological function through transcription of CNTN-1, which is implicated in tumor invasion and metastasis. The expression of VEGF-C was correlated with that of CNTN-1 and cell proliferation and migration induced by VEGF-C were reversed by silencing of CNTN-1. In addition, nude mice inoculated with VEGF-C shRNA-transfected cells exhibited a significantly decreased tumor size in vivo via reduced VEGFR-2 and VEGFR-3 phosphorylation and microvessel formation. VEGF-C upregulation may be involved in esophageal tumor progression. Vector-based RNA interference (RNAi) targeting VEGF-C is a potential therapeutic method for human esophageal carcinoma.
Cytokine 2011 Jul
PMID:VEGF-C promotes the development of esophageal cancer via regulating CNTN-1 expression. 2148 72

The role of chemokines has been extensively analyzed both in cancer risk and tumor progression. Among different cytokines, CXCR4 and its ligand CXCL12 have been recently subjected to a closer examination. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/SDF1-3'A) in the CXCL12 gene and the relative expression of mRNA CXCL12 in peripheral blood were assessed in breast cancer patients, since the chemokine CXCL12 and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using MspI restriction enzyme and the expression analyses by quantitative RT-PCR. No difference in GG genotype and allele A carrier frequencies were observed between breast cancer patients and healthy blood donors and nor when CXCL12 mRNA expression was assessed among patients with different tumor stages. However a significant difference was observed when CXCL12 mRNA relative expression was analyzed in breast cancer patients in accordance to the presence or absence of the CXCL12 rs1801157 allele A. Allele A breast cancer patients presented a mRNA CXCL12 expression about 2.1-fold smaller than GG breast cancer patients. Estrogen positive patients presenting CXCL12 allele A presented a significantly lower expression of CXCL12 in peripheral blood (p=0.039) than GG hormone positive patients. Our findings demonstrated that allele A is associated with low expression of CXCL12 in the peripheral blood from ER-positive breast cancer patients, which suggests implications on breast cancer clinical outcome.
Cytokine 2011 Aug
PMID:CXCL12 rs1801157 polymorphism and expression in peripheral blood from breast cancer patients. 2159 19


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