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Periostin: a potent chemotactic factor for recruiting tumor-associated macrophage.

Wu T, Luo Q, Ouyang G - Protein Cell (2015)

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361102, China.

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The authors further confirmed that POSTN is preferentially expressed and secreted by GSCs in human GBMs. Moreover, TAMs are enriched in POSTN-abundant regions in primary human GBM tissues, indicating that TAM density is positively related to POSTN level in human GBMs. Furthermore, knockdown of POSTN in GSCs significantly inhibits tumor growth and prolongs the survival of mice bearing GSC-derived GBM xenografts... POSTN can activate Akt in macrophages, and anti-αvβ3 integrin antibody blocks this activation... Remarkably, treating primed U937 cells and GSC-derived GBM xenografts with integrin-inhibitory RGD peptide significantly attenuates POSTN-induced macrophage recruitment and decreases TAM density in GSC-derived GBM xenografts... To determine the origin of TAMs in GBMs, Zhou et al. analyzed the specific macrophage markers in GSC-derived xenografts as well as in primary GBM tumors... The authors found that the majority of macrophages are resident microglia (CX3CR1/CCR2) in the normal mouse brain, whereas only CCR2/CX3CR1 macrophages, the monocyte-derived macrophages from the peripheral blood, are found in the GSC-derived GBM xenografts... Knockdown of POSTN in GSCs markedly reduces M2 TAMs in GBM tumors, whereas overexpression of POSTN in GSCs promotes M2 TAM recruitment and augments xenograft growth... Furthermore, POSTN is also able to inhibit macrophage maturation... In addition, intracranial co-transplantation of M2 TAMs with GSCs significantly promotes tumor growth and shortens the survival of mice compared with the transplantation of GSCs alone... GSCs have the ability to transdifferentiate into pericytes and endothelial cells in GBMs (Ricci-Vitiani et al., ; Wang et al., ; Cheng et al., ; Liu and Ouyang, ), but whether these GSC-derived pericytes and endothelial cells still secrete POSTN and have the potential to recruit TAMs, similar to GSCs, is unknown... GSCs can secrete POSTN to recruit TAMs in GBMs, and POSTN knockdown significantly decreases TAMs in GSC-derived xenografts, but whether POSTN can act as a chemoattractant to recruit TAMs or other cells in other tumors remains to be determined... The finding of Zhou et al. that targeting POSTN significantly inhibits GBM tumor growth, mainly by reducing TAM recruitment and inducing massive apoptosis in GSC-derived xenografts, indicates that targeting POSTN-mediated TAM recruitment may improve GBM treatment... Interestingly, continuous anti-macrophage therapy with CCL2 neutralization by blocking the binding of CCL2 to CCR2-expressing monocytes impairs monocyte infiltration into primary mammary tumors and lung metastases in mice (Qian et al., )... However, a recent report demonstrated that cessation of anti-CCL2 therapy unexpectedly results in accelerated lung metastasis in mice (Bonapace et al., )... Considering that silencing POSTN expression has no marked direct impact on the GSC population, cancer cell proliferation or vascular density in tumor bulk, we do not know whether TAM recruitment will rapidly rebound in tumors and lead to lethal relapse after withdrawal of POSTN-targeting therapy... Therefore, targeting POSTN-mediated TAM recruitment may be more effective in fighting GBMs when used in synergy with other therapies.

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Glioma stem cells (GSCs) secrete periostin (POSTN) to recruit and educate macrophages in glioblastoma (GBM). Tumor-associated macrophages (TAMs) are enriched in the POSTN-abundant perivascular niche in GBMs. GSC-secreted POSTN acts as a chemoattractant to recruit and maintain monocyte-derived M2 TAMs from the peripheral blood to promote GBM growth
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Fig1: Glioma stem cells (GSCs) secrete periostin (POSTN) to recruit and educate macrophages in glioblastoma (GBM). Tumor-associated macrophages (TAMs) are enriched in the POSTN-abundant perivascular niche in GBMs. GSC-secreted POSTN acts as a chemoattractant to recruit and maintain monocyte-derived M2 TAMs from the peripheral blood to promote GBM growth

Mentions: Glioblastoma (GBM) is the most common malignant primary brain tumor with a low five-year survival rate. Evidence from experimental and clinical studies indicates that glioma stem cells (GSCs) contribute to GBM tumor growth, therapeutic resistance and relapse (Bao et al., 2006; Gilbertson and Rich, 2007). GSCs are enriched in a unique microenvironment known as the perivascular niche. Interestingly, a large number of tumor-associated macrophages (TAMs) are also distributed in the perivascular niche, indicating that crosstalk between GSCs and TAMs may have a critical role in GBM tumor progression. TAMs are abundant in most solid tumors and contribute to tumor progression in several ways, such as promoting invasion, angiogenesis and immunosuppression; however, the molecular link between TAM recruitment and GSCs has remained generally unclear. Writing in Nature Cell Biology, Zhou et al. provide new insights into where and how TAMs are recruited and educated by GSCs in GBMs (Zhou et al., 2015) (Fig. 1).Figure 1


Periostin: a potent chemotactic factor for recruiting tumor-associated macrophage.

Wu T, Luo Q, Ouyang G - Protein Cell (2015)

Glioma stem cells (GSCs) secrete periostin (POSTN) to recruit and educate macrophages in glioblastoma (GBM). Tumor-associated macrophages (TAMs) are enriched in the POSTN-abundant perivascular niche in GBMs. GSC-secreted POSTN acts as a chemoattractant to recruit and maintain monocyte-derived M2 TAMs from the peripheral blood to promote GBM growth
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4383753&req=5

Fig1: Glioma stem cells (GSCs) secrete periostin (POSTN) to recruit and educate macrophages in glioblastoma (GBM). Tumor-associated macrophages (TAMs) are enriched in the POSTN-abundant perivascular niche in GBMs. GSC-secreted POSTN acts as a chemoattractant to recruit and maintain monocyte-derived M2 TAMs from the peripheral blood to promote GBM growth
Mentions: Glioblastoma (GBM) is the most common malignant primary brain tumor with a low five-year survival rate. Evidence from experimental and clinical studies indicates that glioma stem cells (GSCs) contribute to GBM tumor growth, therapeutic resistance and relapse (Bao et al., 2006; Gilbertson and Rich, 2007). GSCs are enriched in a unique microenvironment known as the perivascular niche. Interestingly, a large number of tumor-associated macrophages (TAMs) are also distributed in the perivascular niche, indicating that crosstalk between GSCs and TAMs may have a critical role in GBM tumor progression. TAMs are abundant in most solid tumors and contribute to tumor progression in several ways, such as promoting invasion, angiogenesis and immunosuppression; however, the molecular link between TAM recruitment and GSCs has remained generally unclear. Writing in Nature Cell Biology, Zhou et al. provide new insights into where and how TAMs are recruited and educated by GSCs in GBMs (Zhou et al., 2015) (Fig. 1).Figure 1

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361102, China.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The authors further confirmed that POSTN is preferentially expressed and secreted by GSCs in human GBMs. Moreover, TAMs are enriched in POSTN-abundant regions in primary human GBM tissues, indicating that TAM density is positively related to POSTN level in human GBMs. Furthermore, knockdown of POSTN in GSCs significantly inhibits tumor growth and prolongs the survival of mice bearing GSC-derived GBM xenografts... POSTN can activate Akt in macrophages, and anti-αvβ3 integrin antibody blocks this activation... Remarkably, treating primed U937 cells and GSC-derived GBM xenografts with integrin-inhibitory RGD peptide significantly attenuates POSTN-induced macrophage recruitment and decreases TAM density in GSC-derived GBM xenografts... To determine the origin of TAMs in GBMs, Zhou et al. analyzed the specific macrophage markers in GSC-derived xenografts as well as in primary GBM tumors... The authors found that the majority of macrophages are resident microglia (CX3CR1/CCR2) in the normal mouse brain, whereas only CCR2/CX3CR1 macrophages, the monocyte-derived macrophages from the peripheral blood, are found in the GSC-derived GBM xenografts... Knockdown of POSTN in GSCs markedly reduces M2 TAMs in GBM tumors, whereas overexpression of POSTN in GSCs promotes M2 TAM recruitment and augments xenograft growth... Furthermore, POSTN is also able to inhibit macrophage maturation... In addition, intracranial co-transplantation of M2 TAMs with GSCs significantly promotes tumor growth and shortens the survival of mice compared with the transplantation of GSCs alone... GSCs have the ability to transdifferentiate into pericytes and endothelial cells in GBMs (Ricci-Vitiani et al., ; Wang et al., ; Cheng et al., ; Liu and Ouyang, ), but whether these GSC-derived pericytes and endothelial cells still secrete POSTN and have the potential to recruit TAMs, similar to GSCs, is unknown... GSCs can secrete POSTN to recruit TAMs in GBMs, and POSTN knockdown significantly decreases TAMs in GSC-derived xenografts, but whether POSTN can act as a chemoattractant to recruit TAMs or other cells in other tumors remains to be determined... The finding of Zhou et al. that targeting POSTN significantly inhibits GBM tumor growth, mainly by reducing TAM recruitment and inducing massive apoptosis in GSC-derived xenografts, indicates that targeting POSTN-mediated TAM recruitment may improve GBM treatment... Interestingly, continuous anti-macrophage therapy with CCL2 neutralization by blocking the binding of CCL2 to CCR2-expressing monocytes impairs monocyte infiltration into primary mammary tumors and lung metastases in mice (Qian et al., )... However, a recent report demonstrated that cessation of anti-CCL2 therapy unexpectedly results in accelerated lung metastasis in mice (Bonapace et al., )... Considering that silencing POSTN expression has no marked direct impact on the GSC population, cancer cell proliferation or vascular density in tumor bulk, we do not know whether TAM recruitment will rapidly rebound in tumors and lead to lethal relapse after withdrawal of POSTN-targeting therapy... Therefore, targeting POSTN-mediated TAM recruitment may be more effective in fighting GBMs when used in synergy with other therapies.

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Related in: MedlinePlus