Cytokine & Growth Factor Reviews RSS feed: Current Issue. Cytokine & Growth Factor Reviews publishes thought-provoking articles (critical reviews, state-of-the-art reviews, letters to the editor, meeting reviews) devoted to important advances in the rapidly changing fields of growth factor and cytokine research. Major emphasis is placed on the multidisciplinary significance of cytokines and growth factors in areas as diverse as signal transduction, cell growth and differentiation, embryonic development, immunology, tumorigenesis and clinical medicine.http://www.cgfr.co.uk/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. All rights reserved. Cytokine & Growth Factor Reviews1359-6101211February 2010 © 2010 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.cgfr.co.uk/article/PIIS1359610110000031/abstract?rss=yesEditorial Board10.1016/S1359-6101(10)00003-1Cytokine & Growth Factor Reviews 21, 1 (2010)2010-02-01Cytokine & Growth Factor Reviews2010-02-01211S1359-6101(10)X0002-8CO2CO2http://www.cgfr.co.uk/article/PIIS1359610109001117/abstract?rss=yesThe concept that certain forms of chronic and persistent inflammation contribute to cancer development was formulated in the 19th century . Experimental and clinical studies have now confirmed this hypothesis and led to a generally accepted paradigm . Epidemiological studies identified chronic infections and inflammation as major risk factors for various types of cancer. Indeed it is estimated that underlying infections and inflammatory reactions are linked to 15–20% of all cancer deaths. In population-based studies prolonged usage of aspirin or of more selective COX-2 inhibitors delay the development of pre-malignant adenomas and may also reduce incidence of different forms of neoplasia.ForewordFrances Balkwill, Alberto Mantovani10.1016/j.cytogfr.2009.11.004Cytokine & Growth Factor Reviews 21, 1 (2010)2009-12-25Cytokine & Growth Factor Reviews2009-12-25211S1359-6101(10)X0002-811http://www.cgfr.co.uk/article/PIIS1359610109001099/abstract?rss=yesAbstract: The classic view that the role of immune cells in cancer is primarily one of tumor rejection has been supplanted by a more complex view of leukocytes having both pro- and anti-tumor properties. This shift is due to the now well recognized capabilities of several myeloid cell types that foster pro-tumor programming of premalignant tissue, as well as the discovery that subsets of leukocytes also suppress development and effector functions of lymphocytes important for mediating anti-tumor immunity. In this review, we focus on the underappreciated role that T lymphocytes play in promoting tumor development. This includes, in addition to the role of T regulatory cells, a role for natural killer T cells and CD4+ T helper cells in suppressing anti-tumor immunity and promoting cancer growth and metastasis.Lymphocytes in cancer development: Polarization towards pro-tumor immunityBrian Ruffell, David G. DeNardo, Nesrine I. Affara, Lisa M. Coussens10.1016/j.cytogfr.2009.11.002Cytokine & Growth Factor Reviews 21, 1 (2010)2009-12-14Cytokine & Growth Factor Reviews2009-12-14211S1359-6101(10)X0002-8310http://www.cgfr.co.uk/article/PIIS1359610109001129/abstract?rss=yesAbstract: Transcriptional factors of the NF-κB family and STAT3 are ubiquitously expressed and control numerous physiological processes including development, differentiation, immunity, metabolism and cancer. Both NF-κB and STAT3 are rapidly activated in response to various stimuli including stresses and cytokines, although they are regulated by entirely different signaling mechanisms. Once activated, NF-κB and STAT3 control the expression of anti-apoptotic, pro-proliferative and immune response genes. Some of these genes overlap and require transcriptional cooperation between the two factors. The activation of and interaction between STAT3 and NF-κB plays a key role in controlling the dialog between the malignant cell and its microenvironment, especially with inflammatory/immune cells that infiltrate tumors. Quite often, cytokines whose expression is induced in response to NF-κB in immune cells of the tumor microenvironment lead to STAT3 activation in both malignant and immune cells. While within malignant and pre-malignant cells STAT3 exerts important oncogenic functions, within inflammatory cells it may also suppress tumor promotion through its anti-inflammatory effects. Other interactions and forms of crosstalk between NF-κB and STAT3 include physical interaction between the two, cooperation of these factors at gene promoters/enhancers, the NF-κB dependent expression of inhibitors of STAT3 activation and the participation of STAT3 in inflammatory cells in the negative regulation NF-κB. Despite these versatile and occasionally antagonistic interactions, NF-κB and STAT3 cooperate to promote the development and progression of colon, gastric and liver cancers. In addition to explaining the molecular pathogenesis of cancer, these interactions also offer opportunities for the design of new therapeutic interventions.Dangerous liaisons: STAT3 and NF-κB collaboration and crosstalk in cancerSergei I. Grivennikov, Michael Karin10.1016/j.cytogfr.2009.11.005Cytokine & Growth Factor Reviews 21, 1 (2010)2009-12-17Cytokine & Growth Factor Reviews2009-12-17211S1359-6101(10)X0002-81119http://www.cgfr.co.uk/article/PIIS1359610109001105/abstract?rss=yesAbstract: FDA approval of several inhibitors of the VEGF pathway has enabled significant advances in the therapy of cancer and neovascular age-related macular degeneration. However, similar to other therapies, inherent/acquired resistance to anti-angiogenic drugs may occur in patients, leading to disease progression. So far the lack of predictive biomarkers has precluded identification of patients most likely to respond to such treatments. Recent suggest that both tumor and non-tumor (stromal) cell types are involved in the reduced responsiveness to the treatments. The present review examines the role of tumor- as well as stromal cell-derived pathways involved in tumor growth and in refractoriness to anti-VEGF therapies.Pathways mediating VEGF-independent tumor angiogenesisNapoleone Ferrara10.1016/j.cytogfr.2009.11.003Cytokine & Growth Factor Reviews 21, 1 (2010)2009-12-11Cytokine & Growth Factor Reviews2009-12-11211S1359-6101(10)X0002-82126http://www.cgfr.co.uk/article/PIIS1359610109001142/abstract?rss=yesAbstract: Chemokines are a key component of cancer-related inflammation. Chemokines and chemokine receptors are downstream of genetic events that cause neoplastic transformation and are components of chronic inflammatory conditions, which predispose to cancer. Components of the chemokine system affect in a cell autonomous or non-autonomous way multiple pathways of tumor progression, including: leukocyte recruitment and function; cellular senescence; tumor cell proliferation and survival; invasion and metastasis. Available information in preclinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies.The chemokine system in cancer biology and therapyAlberto Mantovani, Benedetta Savino, Massimo Locati, Luca Zammataro, Paola Allavena, Raffaella Bonecchi10.1016/j.cytogfr.2009.11.007Cytokine & Growth Factor Reviews 21, 1 (2010)2009-12-09Cytokine & Growth Factor Reviews2009-12-09211S1359-6101(10)X0002-82739http://www.cgfr.co.uk/article/PIIS1359610109001166/abstract?rss=yesAbstract: CCL2 is a chemokine known to recruit monocytes and macrophages to sites of inflammation. A growing body of research suggests CCL2 is progressively overexpressed in tumor beds and may play a role in the clinical progression of solid tumors. Cancer cells derived from several solid tumor types demonstrate functional receptors for CCL2, suggesting this chemokine may achieve tumorigenicity through direct effects on malignant cells; however, a variety of normal host cells that co-exist with cancer in the tumor microenvironment also respond to CCL2. These cells include macrophages, osteoclasts, endothelial cells, T-lymphocytes, and myeloid-derived immune suppressor cells (MDSCs). CCL2 mediated interactions between normal and malignant cells in the tumor microenvironment and plays a multi-faceted role in tumor progression.CC chemokine ligand 2 (CCL2) promotes prostate cancer tumorigenesis and metastasisJian Zhang, Lalit Patel, Kenneth J. Pienta10.1016/j.cytogfr.2009.11.009Cytokine & Growth Factor Reviews 21, 1 (2010)2009-12-14Cytokine & Growth Factor Reviews2009-12-14211S1359-6101(10)X0002-84148http://www.cgfr.co.uk/article/PIIS1359610109001154/abstract?rss=yesAbstract: The transforming growth factor beta (TGF-β) 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-β has been shown to inhibit epithelial cell cycle progression and promote apoptosis that together significantly contribute to the tumor suppressive role for TGF-β during carcinoma initiation and progression. TGF-β 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-β stimulation can also promote metastasis. Interestingly, enhanced metastasis in the absence of a carcinoma cell response to TGF-β 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-β in immune suppression since the MDSCs are an abundant source of TGF-β production. Importantly, it is now clear that carcinoma-immune cell cross-talk initiated by TGF-β signaling within the carcinoma cell is a significant determinant worth consideration when designing therapeutic strategies to manage tumor progression and metastasis.Transforming growth factor beta (TGF-β) and inflammation in cancerBrian Bierie, Harold L. Moses10.1016/j.cytogfr.2009.11.008Cytokine & Growth Factor Reviews 21, 1 (2010)2009-12-17Cytokine & Growth Factor Reviews2009-12-17211S1359-6101(10)X0002-84959http://www.cgfr.co.uk/article/PIIS1359610109001130/abstract?rss=yesAbstract: 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.The resolution of inflammation and cancerJuan Rodriguez-Vita, Toby Lawrence10.1016/j.cytogfr.2009.11.006Cytokine & Growth Factor Reviews 21, 1 (2010)2009-12-21Cytokine & Growth Factor Reviews2009-12-21211S1359-6101(10)X0002-86165http://www.cgfr.co.uk/article/PIIS1359610109001178/abstract?rss=yesAbstract: 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.Matricellular proteins and inflammatory cells: A task force to promote or defeat cancer?Andrea Sabina Llera, Maria Romina Girotti, Lorena Gabriela Benedetti, Osvaldo Luis Podhajcer10.1016/j.cytogfr.2009.11.010Cytokine & Growth Factor Reviews 21, 1 (2010)2009-12-14Cytokine & Growth Factor Reviews2009-12-14211S1359-6101(10)X0002-86776http://www.cgfr.co.uk/article/PIIS1359610109001087/abstract?rss=yesAbstract: 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.Molecular mechanisms of perineural invasion, a forgotten pathway of dissemination and metastasisFederica Marchesi, Lorenzo Piemonti, Alberto Mantovani, Paola Allavena10.1016/j.cytogfr.2009.11.001Cytokine & Growth Factor Reviews 21, 1 (2010)2010-01-11Cytokine & Growth Factor Reviews2010-01-11211S1359-6101(10)X0002-87782