Chemokines, chemokine receptors, and cancer metastasis

Kakinuma, Takashi; Hwang, Samuel T

doi:10.1189/jlb.1105633

Cited by 305 publications

(258 citation statements)

References 111 publications

(119 reference statements)

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“…[10][11][12][13][14][15][16][17] We found that CXCR3 expression in LNCaP cells was decreased after 6 hr of AG treatment, but this suppressive effect was short lived and the receptor expression recovered after 24 hr. In case of PC3 and DU-145 cells, reduced expression of CXCR3 was maintained from 6 to 24 hr after AG treatment.…”

Section: Ag Modulates Chemokine Expression In Pca Cellsmentioning

confidence: 68%

“…Cytokines mediated signals can cross talk with chemokines and multiple chemokine-receptors are shown to be associated with tumor progression and metastasis. [7][8][9][10][11][12][13][14][15][16][17] Additionally, cell cycle regulation is governed by calcium flux, which in turn is altered by chemokine signaling. In this manuscript we have presented evidence that AG exerts its anticancer effects by modulating cell cycle as well as chemokine receptors (CXCR3 and CXCR7) and their common ligand CXCL11 in PCa cells.…”

Section: Introductionmentioning

confidence: 99%

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Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors

et al. 2016

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Despite state of the art cancer diagnostics and therapies offered in clinic, prostate cancer (PCa) remains the second leading cause of cancer-related deaths. Hence, more robust therapeutic/preventive regimes are required to combat this lethal disease. In the current study, we have tested the efficacy of Andrographolide (AG), a bioactive diterpenoid isolated from Andrographis paniculata, against PCa. This natural agent selectively affects PCa cell viability in a dose and time-dependent manner, without affecting primary prostate epithelial cells. Furthermore, AG showed differential effect on cell cycle phases in LNCaP, C4-2b and PC3 cells compared to retinoblastoma protein (RB ¡/¡ ) and CDKN2A lacking DU-145 cells. G2/M transition was blocked in LNCaP, C4-2b and PC3 after AG treatment whereas DU-145 cells failed to transit G1/S phase. This difference was primarily due to differential activation of cell cycle regulators in these cell lines. Levels of cyclin A2 after AG treatment increased in all PCa cells line. Cyclin B1 levels increased in LNCaP and PC3, decreased in C4-2b and showed no difference in DU-145 cells after AG treatment. AG decreased cyclin E2 levels only in PC3 and DU-145 cells. It also altered Rb, H3, Wee1 and CDC2 phosphorylation in PCa cells. Intriguingly, AG reduced cell viability and the ability of PCa cells to migrate via modulating CXCL11 and CXCR3 and CXCR7 expression. The significant impact of AG on cellular and molecular processes involved in PCa progression suggests its potential use as a therapeutic and/or preventive agent for PCa.

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Section: Ag Modulates Chemokine Expression In Pca Cellsmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors

et al. 2016

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“…It is becoming increasingly clear that many members of this family regulate a complex milieu of interactions between tumor cells, stromal cells, tumor infiltrating leukocytes and endothelial cells and that better understanding of the specific actions of chemokines and their receptors in promoting malignancy will significantly contribute to combating cancer. 2 CXCR4 and CCR7 are the major chemokine receptors found on a wide range of tumor cells and high levels of these receptors are associated with higher grade and poor prognosis of breast, lung, colon and other cancers. 3 Blocking the interaction between CXCR4 and its ligand CXCL12, dramatically reduces breast and other cancer metastases in mouse models.…”

mentioning

confidence: 99%

“…However, more recent evidence also supports other roles for chemokine GPCRs including cell growth, adhesion to endothelium and extravasation. 2 Yet specific, non-redundant signaling events and cellular functions directly linking these surface molecules with cancer metastasis are still largely unknown. 6 Anoikis is apoptosis induced upon perturbation or loss of cell-matrix interactions.…”

mentioning

confidence: 99%

Chemokine receptors CXCR4 and CCR7 promote metastasis by preventing anoikis in cancer cells

2009

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Chemokine receptors are essential mediators of the metastatic spread in various cancer types; however their precise function in the development of secondary tumors remains poorly understood. We report here a novel property of the chemokine receptors CXCR4 and CCR7 in inhibiting detachment-induced cell death -anoikis, which is believed to be one of the major blocks in the metastatic spread of various neoplasms. Activation of these chemokine receptors by their respective ligands, CXCL12 and CCL21 specifically reduced the sensitivity of metastatic breast cancer cells to anoikis by a distinct mechanism of selective regulation of pro-apoptotic Bmf and anti-apoptotic Bcl-xL proteins. Consequently, functional CXCR4 and CCR7 increased cell survival in the absence of correct ECM attachment both in vitro and in vivo. We also demonstrated that preventing chemokineinduced reduction in Bmf levels significantly attenuated breast cancer metastasis in an experimental mouse model. These results provide evidence for a previously unknown axis in malignant tumors, which connects chemokine receptors with deregulated apoptosis in the absence of the appropriate cell -ECM interaction and may offer novel targets for therapeutic intervention for the treatment of metastatic breast and potentially other tumors. Cell Death and Differentiation (2009) 16, 664-673; doi:10.1038/cdd.2008; published online 9 January 2009The main cause of cancer-related deaths is the spread of tumor cells to sites distant from the primary locus and the subsequent establishment of secondary lesions. The heterogeneity and complexity of malignant transformation make it difficult to identify common molecular mechanisms governing the metastatic progression of cancer and potentially account for the lack of effective treatments for malignant cancers. Recently, members of the chemokine receptor family of G-protein-coupled receptors (GPCRs) have been assigned a major role in this process (reviewed in Zlotnik 1 ). It is becoming increasingly clear that many members of this family regulate a complex milieu of interactions between tumor cells, stromal cells, tumor infiltrating leukocytes and endothelial cells and that better understanding of the specific actions of chemokines and their receptors in promoting malignancy will significantly contribute to combating cancer. 2 CXCR4 and CCR7 are the major chemokine receptors found on a wide range of tumor cells and high levels of these receptors are associated with higher grade and poor prognosis of breast, lung, colon and other cancers. 3 Blocking the interaction between CXCR4 and its ligand CXCL12, dramatically reduces breast and other cancer metastases in mouse models. 4 Our recent results have also provided a direct correlation between functional activation of CXCR4 and CCR7 and the invasive, metastatic phenotype of breast cancer cells 5 further supporting a highly important role for these molecules in tumor dissemination to distant sites. Initial studies suggested that these surface molecules induce directional migration of ma...

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“…8,34 Several recent studies have implicated the involvement of chemokine receptors and their ligands in the potential mechanisms of cancer metastasis. [35][36][37][38] Expression of CXCR-4 and its ligand CXCL-12 play a key role in cell adhesion, migration and activation of melanomas. [39][40][41] Several adhesion molecules are involved in the metastatic process 42 including CD44, intercellular cell adhesion molecule 1 (ICAM-1, CD54) and neural cell adhesion molecule (NCAM, CD56).…”

mentioning

confidence: 99%

Locally generated VGVAPG and VAPG elastin‐derived peptides amplify melanoma invasion via the galectin‐3 receptor

Pócza

Süli‐Vargha

Darvas

et al. 2008

Intl Journal of Cancer

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Melanomas containing more elastin are associated with higher stages of the disease. The interaction between elastin-derived peptides and melanoma cells appears to play an important role in the progression of melanomas. The effects of the elastin-derived peptides VGVAPG and VAPG have been investigated on the migration, invasion, adhesion and angiogenesis of human melanoma cells of different invasive potential. Elastin, tropoelastin and VGVAPG peptide were demonstrated at the invasion site of melanoma using histochemistry and immunohistochemistry. Not only the VGVAPG elastin-derived peptide, which exhibits the XGXXPG consensus sequence in its primary structure, but also the shorter VAPG bind directly to 3 cell surface receptors: galectin-3, integrin avb3 and elastin-binding protein. Our results suggest that the increased levels of elastin-derived peptides facilitate the invasion of melanoma cells: (i) VGVAPG and VAPG elastin-derived peptides are chemotactic for melanoma cells; (ii) they can increase the migration of melanoma cells and the expression of CXCR-4 and CXCL-12 chemokines; (iii) they enhance the expression of the elastin-degrading MMP-2 and MMP-3; (iv) they increase the attachment of melanoma cells and the expression of different adhesion molecules; (v) they increase the expression of the lymphangiogenic VEGF-C and (vi) the galectin-3 receptor can mediate all these effects. Clinical and therapeutic aspects are also discussed. ' 2007 Wiley-Liss, Inc.Key words: melanoma; invasion; elastin; galectin-3 Recently, the incidence of melanomas has significantly increased, and patients have a reduced life expectancy. 1 Malignant melanomas are characterized as tumors of aggressive biological behavior with high motility and metastatic potential. 2,3 The extracellular matrix (ECM) plays a key role in the growth and invasion of tumor cells. Melanoma cells specifically interact with unique matrix proteins such as elastin, especially in elastin-rich organs such as the skin, lung and blood vessels. 4,5 Melanomas containing more elastin are associated with higher stages of the disease: lymph node or distant metastases, higher Clark-level and greater tumor thickness. 6 Several enzymes belonging to the matrix metalloproteinases (MMPs), serine and cysteine proteases superfamily mediate the degradation of elastin. [7][8][9] The level of these enzymes is increased in various stages of the disease 10,11 and leads to the generation of elastin-derived peptides (EDPs), which alter tissue homeostasis. EDPs have several biological effects on a wide range of cells including normal and tumor cells, 12 for example cell proliferation, 13,14 migration and chemotaxis, 15,16 tumor progression, 5,17-20 endothelial cell migration and angiogenesis. 21 These effects of EDPs are mediated predominantly by 3 cellsurface receptors: elastin binding protein (EBP), integrin avb3 and galectin-3 receptors. EBP is a 67-kDa multifunctional receptor containing lectin-binding site [22][23][24][25] and further identified as an enzymatically inactive form of...

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Chemokines, chemokine receptors, and cancer metastasis

Cited by 305 publications

References 111 publications

Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors

Andrographolide inhibits prostate cancer by targeting cell cycle regulators, CXCR3 and CXCR7 chemokine receptors

Chemokine receptors CXCR4 and CCR7 promote metastasis by preventing anoikis in cancer cells

Locally generated VGVAPG and VAPG elastin‐derived peptides amplify melanoma invasion via the galectin‐3 receptor

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