High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time.
Mucin 2 (MUC2) is a mucin molecule aberrantly expressed by ovarian cancer cells. Previous in vitro studies have indicated that MUC2 promotes cancer growth and metastasis through a tumor-associated macrophage (TAM)-dependent mechanism. However, this mechanism has never been linked to clinical oncolog...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3855613?pdf=render |
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| author | Yi-feng He Mei-ying Zhang Xin Wu Xiang-jun Sun Ting Xu Qi-zhi He Wen Di |
| author_facet | Yi-feng He Mei-ying Zhang Xin Wu Xiang-jun Sun Ting Xu Qi-zhi He Wen Di |
| author_sort | Yi-feng He |
| collection | DOAJ |
| description | Mucin 2 (MUC2) is a mucin molecule aberrantly expressed by ovarian cancer cells. Previous in vitro studies have indicated that MUC2 promotes cancer growth and metastasis through a tumor-associated macrophage (TAM)-dependent mechanism. However, this mechanism has never been linked to clinical oncology, and its prognostic significance needed to be clarified. Here, we collected 102 consecutive ovarian cancer specimens and used the multiple immuno-histo-chemical/-fluorescent technique to determine the correlations between the MUC2 expression status, the ratio of M1/M2 TAMs and the densities of cyclooxygenase-2 (COX-2)(+) TAMs and COX-2(+) cancer cells. The Kaplan-Meier survival analysis and multivariate Cox regression analysis were used to evaluate the prognostic influences of these parameters. As a result, we found that the MUC2 overexpression (immunostaining ++/+++) was significantly correlated with a reduced ratio of M1/M2 TAMs (p<0.001), an increased density of COX-2(+) TAMs (p<0.001) and an increased density of COX-2(+) cancer cells (p=0.017). Moreover, most of the M2 TAMs (93%-100%) and COX-2(+) TAMs (63%-89%) overlapped; and the COX-2(+) cancer cells were frequently observed near the COX-2(+) TAMs. In the Cox regression analysis, MUC2 overexpression was found to be an independent prognostic factor for ovarian cancer patients, of which the hazard ratio (HR) was 2.354 (95% confidence interval (CI): 1.031-10.707, p=0.005). Also, the reduced ratio of M1/M2 TAMs and the increased densities of COX-2(+) TAMs and COX-2(+) cancer cells were demonstrated to be the predictors of poor prognosis, among which the reduced M1/M2 ratio possessed the highest HR (1.767, 95% CI: 1.061-6.957, p=0.019). All these findings revealed that MUC2 can concurrently exert M2-polarizing and COX-2-inducing effects on TAMs, by which it causes an imbalanced TAM M1-/M2-polarization pattern and induces local PGE2 synthesis (in both TAMs and cancer cells). The positive feedback between local PGE2 synthesis and TAM M2-polarization accelerates ovarian cancer progression. |
| first_indexed | 2024-12-20T07:40:56Z |
| format | Article |
| id | doaj.art-81a2dcebaa8c4d1eb6aa02956e570277 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T07:40:56Z |
| publishDate | 2013-01-01 |
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| spelling | doaj.art-81a2dcebaa8c4d1eb6aa02956e5702772022-12-21T19:48:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e7976910.1371/journal.pone.0079769High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time.Yi-feng HeMei-ying ZhangXin WuXiang-jun SunTing XuQi-zhi HeWen DiMucin 2 (MUC2) is a mucin molecule aberrantly expressed by ovarian cancer cells. Previous in vitro studies have indicated that MUC2 promotes cancer growth and metastasis through a tumor-associated macrophage (TAM)-dependent mechanism. However, this mechanism has never been linked to clinical oncology, and its prognostic significance needed to be clarified. Here, we collected 102 consecutive ovarian cancer specimens and used the multiple immuno-histo-chemical/-fluorescent technique to determine the correlations between the MUC2 expression status, the ratio of M1/M2 TAMs and the densities of cyclooxygenase-2 (COX-2)(+) TAMs and COX-2(+) cancer cells. The Kaplan-Meier survival analysis and multivariate Cox regression analysis were used to evaluate the prognostic influences of these parameters. As a result, we found that the MUC2 overexpression (immunostaining ++/+++) was significantly correlated with a reduced ratio of M1/M2 TAMs (p<0.001), an increased density of COX-2(+) TAMs (p<0.001) and an increased density of COX-2(+) cancer cells (p=0.017). Moreover, most of the M2 TAMs (93%-100%) and COX-2(+) TAMs (63%-89%) overlapped; and the COX-2(+) cancer cells were frequently observed near the COX-2(+) TAMs. In the Cox regression analysis, MUC2 overexpression was found to be an independent prognostic factor for ovarian cancer patients, of which the hazard ratio (HR) was 2.354 (95% confidence interval (CI): 1.031-10.707, p=0.005). Also, the reduced ratio of M1/M2 TAMs and the increased densities of COX-2(+) TAMs and COX-2(+) cancer cells were demonstrated to be the predictors of poor prognosis, among which the reduced M1/M2 ratio possessed the highest HR (1.767, 95% CI: 1.061-6.957, p=0.019). All these findings revealed that MUC2 can concurrently exert M2-polarizing and COX-2-inducing effects on TAMs, by which it causes an imbalanced TAM M1-/M2-polarization pattern and induces local PGE2 synthesis (in both TAMs and cancer cells). The positive feedback between local PGE2 synthesis and TAM M2-polarization accelerates ovarian cancer progression.http://europepmc.org/articles/PMC3855613?pdf=render |
| spellingShingle | Yi-feng He Mei-ying Zhang Xin Wu Xiang-jun Sun Ting Xu Qi-zhi He Wen Di High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time. PLoS ONE |
| title | High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time. |
| title_full | High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time. |
| title_fullStr | High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time. |
| title_full_unstemmed | High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time. |
| title_short | High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time. |
| title_sort | high muc2 expression in ovarian cancer is inversely associated with the m1 m2 ratio of tumor associated macrophages and patient survival time |
| url | http://europepmc.org/articles/PMC3855613?pdf=render |
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