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Fatal attraction: How macrophages participate in tumor metastases.

Gabrilovich D - J. Exp. Med. (2015)

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Affiliation: The Wistar Institute dgabrilovich@wistar.org.

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Now, Kitamura et al., using mouse models of breast cancer, have uncovered a major role for a CCL2-induced chemokine cascade that supports macrophage recruitment and retention in metastatic sites in the lung... This raised the attractive possibility of controlling metastasis by targeting CCL2... However, an anti-CCL2 antibody was found to be ineffective in humans... Furthermore, loss of CCL2 signaling reduced the numbers of circulating monocytes, leading to an increased susceptibility to infection in mouse models... This necessitated the search for more precise mechanisms regulating MAM migration, as addressed by Kitamura et al. in the current study... Kitamura et al. found that MAMs expressed the CCL2 receptor CCR2, and activation of CCR2 signaling prompted MAMs to secrete another chemokine, CCL3... The increased CCL3 secretion resulted in enhanced MAM–cancer cell interaction, at least in part through integrin α4, and prolonged the retention of MAMs in the metastatic sites, resulting in extravasation of cancer cells... Although the concept of chemokine crosstalk has been described previously, this work demonstrates, for the first time, the existence of the CCL2–CCL3 cascade in vivo and its contribution to tumor metastases... It also seems likely that CCL2-induced CCL3 expression is specific to the prometastatic macrophage, which raises the exciting possibility of more effective identification and targeting of MAMs. However, the molecular mechanism by which CCL3 activates macrophages and promotes their interaction with tumor cells needs to be elucidated... CCL3 is known to have potent effects on neutrophil extravasation and activation.

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Fatal attraction: How macrophages participate in tumor metastases.

Gabrilovich D - J. Exp. Med. (2015)

Insight from Dmitry Gabrilovich
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493407&req=5

fig1: Insight from Dmitry Gabrilovich

View Article: PubMed Central - HTML - PubMed

Affiliation: The Wistar Institute dgabrilovich@wistar.org.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Now, Kitamura et al., using mouse models of breast cancer, have uncovered a major role for a CCL2-induced chemokine cascade that supports macrophage recruitment and retention in metastatic sites in the lung... This raised the attractive possibility of controlling metastasis by targeting CCL2... However, an anti-CCL2 antibody was found to be ineffective in humans... Furthermore, loss of CCL2 signaling reduced the numbers of circulating monocytes, leading to an increased susceptibility to infection in mouse models... This necessitated the search for more precise mechanisms regulating MAM migration, as addressed by Kitamura et al. in the current study... Kitamura et al. found that MAMs expressed the CCL2 receptor CCR2, and activation of CCR2 signaling prompted MAMs to secrete another chemokine, CCL3... The increased CCL3 secretion resulted in enhanced MAM–cancer cell interaction, at least in part through integrin α4, and prolonged the retention of MAMs in the metastatic sites, resulting in extravasation of cancer cells... Although the concept of chemokine crosstalk has been described previously, this work demonstrates, for the first time, the existence of the CCL2–CCL3 cascade in vivo and its contribution to tumor metastases... It also seems likely that CCL2-induced CCL3 expression is specific to the prometastatic macrophage, which raises the exciting possibility of more effective identification and targeting of MAMs. However, the molecular mechanism by which CCL3 activates macrophages and promotes their interaction with tumor cells needs to be elucidated... CCL3 is known to have potent effects on neutrophil extravasation and activation.

Show MeSH