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Journal ArticleDOI

Chemotaxis in cancer

01 Aug 2011-Nature Reviews Cancer (Nature Publishing Group)-Vol. 11, Iss: 8, pp 573-587
TL;DR: This Review summarizes how chemotaxis directs the different behaviours of tumour cells and stromal cells in vivo, how molecular pathways regulateChemotaxis in tumours and how chemtaxis choreographs cell behaviour to shape the tumour microenvironment and to determine metastatic spread.
Abstract: Chemotaxis of tumour cells and stromal cells in the surrounding microenvironment is an essential component of tumour dissemination during progression and metastasis. This Review summarizes how chemotaxis directs the different behaviours of tumour cells and stromal cells in vivo, how molecular pathways regulate chemotaxis in tumour cells and how chemotaxis choreographs cell behaviour to shape the tumour microenvironment and to determine metastatic spread. The central importance of chemotaxis in cancer progression is highlighted by discussion of the use of chemotaxis as a prognostic marker, a treatment end point and a target of therapeutic intervention.

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Citations
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Journal ArticleDOI
23 Nov 2011-Cell
TL;DR: The cell-matrix and cell-cell adhesion, protease, and cytokine systems that underlie tissue invasion by cancer cells are described and explained to explain how the reciprocal reprogramming of both the tumor cells and the surrounding tissue structures not only guides invasion, but also generates diverse modes of dissemination.

1,693 citations


Cites background from "Chemotaxis in cancer"

  • ...Because of their pleiotropic effects, promigratory conditioning of the tumor-associated tissue increases: (1) the invasion and dissemination of tumor cells; (2) the motility and activity of stromal cells, including fibroblasts and macrophages; (3) the recruitment and transendothelial migration of circulating leukocytes and precursor cells into the tumor stroma; and (4) the mobilization of bone marrow-derived cells into the circulation through systemic growth factor effects in other organs, including the bone marrow (Orimo et al., 2005; Padua and Massagué, 2009; Roussos et al., 2011; Zlotnik et al., 2011)....

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  • ...…and precursor cells into the tumor stroma; and (4) the mobilization of bone marrow-derived cells into the circulation through systemic growth factor effects in other organs, including the bone marrow (Orimo et al., 2005; Padua and Massagué, 2009; Roussos et al., 2011; Zlotnik et al., 2011)....

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Journal ArticleDOI
TL;DR: A framework for addressing potential mechanisms, experimental strategies and technical challenges to study collective cancer cell invasion is proposed.
Abstract: Most invasive solid tumours display predominantly collective invasion, in which groups of cells invade the peritumoral stroma while maintaining cell-cell contacts. As the concepts and experimental models for functional analysis of collective cancer cell invasion are rapidly developing, we propose a framework for addressing potential mechanisms, experimental strategies and technical challenges to study this process.

839 citations

Journal ArticleDOI
TL;DR: Evidence is provided that the endothelium poses a barrier to tumor cell intravasation that can be regulated by factors present in the tumor microenvironment.
Abstract: Entry of tumor cells into the blood stream is a critical step in cancer metastasis. Although significant progress has been made in visualizing tumor cell motility in vivo, the underlying mechanism of cancer cell intravasation remains largely unknown. We developed a microfluidic-based assay to recreate the tumor-vascular interface in three-dimensions, allowing for high resolution, real-time imaging, and precise quantification of endothelial barrier function. Studies are aimed at testing the hypothesis that carcinoma cell intravasation is regulated by biochemical factors from the interacting cells and cellular interactions with macrophages. We developed a method to measure spatially resolved endothelial permeability and show that signaling with macrophages via secretion of tumor necrosis factor alpha results in endothelial barrier impairment. Under these conditions intravasation rates were increased as validated with live imaging. To further investigate tumor-endothelial (TC-EC) signaling, we used highly invasive fibrosarcoma cells and quantified tumor cell migration dynamics and TC-EC interactions under control and perturbed (with tumor necrosis factor alpha) barrier conditions. We found that endothelial barrier impairment was associated with a higher number and faster dynamics of TC-EC interactions, in agreement with our carcinoma intravasation results. Taken together our results provide evidence that the endothelium poses a barrier to tumor cell intravasation that can be regulated by factors present in the tumor microenvironment.

751 citations


Cites background from "Chemotaxis in cancer"

  • ...Cell-cell communication and chemotaxis (5) are key to this process and can occur via paracrine signals and/or direct contact between different cell types during tumor cell invasion (6) and metastatic colonization (7)....

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Journal ArticleDOI
TL;DR: Targeting molecular pathways regulating TAM polarization holds great promise for anticancer therapy.

748 citations

Journal ArticleDOI
TL;DR: How cancer cells cross the endothelial barrier during extravasation is described and how different receptors, signalling pathways and circulating cells such as leukocytes and platelets contribute to this process are described.
Abstract: During metastasis, cancer cells disseminate to other parts of the body by entering the bloodstream in a process that is called intravasation. They then extravasate at metastatic sites by attaching to endothelial cells that line blood vessels and crossing the vessel walls of tissues or organs. This Review describes how cancer cells cross the endothelial barrier during extravasation and how different receptors, signalling pathways and circulating cells such as leukocytes and platelets contribute to this process. Identification of the mechanisms that underlie cancer cell extravasation could lead to the development of new therapies to reduce metastasis.

743 citations

References
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Journal ArticleDOI
25 Nov 2009-Cell
TL;DR: The mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.

8,642 citations


"Chemotaxis in cancer" refers background in this paper

  • ...Tumour cells undergoing epithelial-to-mesenchymal transition (EMT), which is apparent in 10–40% of carcinoma...

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Journal ArticleDOI
TL;DR: The origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit are discussed.
Abstract: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand during cancer, inflammation and infection, and that have a remarkable ability to suppress T-cell responses. These cells constitute a unique component of the immune system that regulates immune responses in healthy individuals and in the context of various diseases. In this Review, we discuss the origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit.

5,811 citations

Journal ArticleDOI
01 Mar 2001-Nature
TL;DR: It is reported that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases and their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis.
Abstract: Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

5,132 citations

Journal ArticleDOI
TL;DR: It is shown, in detailed studies of CD4+CD25+FOXP3+ Treg cells in 104 individuals affected with ovarian carcinoma, that human tumor T Reg cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo.
Abstract: Regulatory T (T(reg)) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen-reactive lymphocytes mediated by T(reg) cells; however, definitive evidence that T(reg) cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4(+)CD25(+)FOXP3(+) T(reg) cells in 104 individuals affected with ovarian carcinoma, that human tumor T(reg) cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo. We also show that tumor T(reg) cells are associated with a high death hazard and reduced survival. Human T(reg) cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T(reg) cells to the tumor. This specific recruitment of T(reg) cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T(reg) cell migration or function may help to defeat human cancer.

4,795 citations


"Chemotaxis in cancer" refers background in this paper

  • ...T Reg cells express the chemokine receptor CCR4 and can be attracted to ovarian cancer cells by the tumour cell- and macrophage-derived chemokine ligand CCL22 (Ref...

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Journal ArticleDOI
TL;DR: The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.
Abstract: Metastatic breast cancer (MBC) is considered incurable; therefore, palliative treatment is the only option. The biologic heterogeneity of the disease is reflected in its somewhat unpredictable clinical behavior. The presence of circulating tumor cells (CTCs) in patients with MBC about to start a new line of treatment has been shown to predict progression-free and overall survival. This prognostic value is independent of the line of therapy (eg, first or second line). Moreover, a multivariate analysis has shown the prognostic value of CTCs to be superior to that of site of metastasis, type of therapy, and length of time to recurrence after definitive primary surgery. These data suggest that the presence of CTCs may be used to modify the staging system for advanced disease. Larger studies are needed to confirm these data and evaluate the use of CTC detection in monitoring treatment and furthering our understanding of breast cancer biology when combined with other diagnostic technologies.

4,244 citations

Trending Questions (2)
What part of chemotaxis in cancer has not been studied yet?

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What part of chemotaxis in breast cancer has not been studied yet?

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