Limits...
Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression.

Yasuoka H, Kodama R, Tsujimoto M, Yoshidome K, Akamatsu H, Nakahara M, Inagaki M, Sanke T, Nakamura Y - BMC Cancer (2009)

Bottom Line: Survival curves determined by the Kaplan-Meier method showed that Nrp2 expression was associated with reduced overall survival.In multivariate analysis, Nrp2 expression emerged as a significant independent predictor for overall survival.Nrp2 expression may serve as a significant prognostic factor for long-term survival in breast cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Laboratory Medicine, Wakayama Medical University, Wakayama, Japan. hyasuoka@mail.wakayama-med.ac.jp

ABSTRACT

Background: Neuropilin-2 (Nrp2) is a receptor for vascular endothelial growth factor-C (VEGF-C), which is a well-known lymphangiogenic factor and plays an important role in lymph node metastasis of various human cancers, including breast cancer. Recently, Nrp2 was shown to play a role in cancer by promoting tumor cell metastasis. CXC chemokine receptor 4 (CXCR4) also promotes tumor metastasis. In the previous studies, we demonstrated that VEGF-C and cytoplasmic CXCR4 expressions were correlated with poorer patient prognosis (BMC Cancer 2008,8:340; Breast Cancer Res Treat 2005, 91:125-132).

Methods: The relationship between Nrp2 expression and lymph node metastasis, VEGF-C expression, CXCR4 expression, and other established clinicopathological variables (these data were cited in our previous papers), including prognosis, was analyzed in human breast cancer. Effects of neutralizing anti-Nrp2 antibody on CXCR4 expression and chemotaxis were assessed in MDA-MB-231 breast cancer cells.

Results: Nrp2 expression was observed in 53.1% (60 of 113) of the invasive breast carcinomas. Nrp2 expression was significantly correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Survival curves determined by the Kaplan-Meier method showed that Nrp2 expression was associated with reduced overall survival. In multivariate analysis, Nrp2 expression emerged as a significant independent predictor for overall survival. Neutralizing anti-Nrp2 antibody blocks cytoplasmic CXCR4 expression and CXCR4-induced migration in MDA-MB-231 cells.

Conclusion: Nrp2 expression was correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Nrp2 expression may serve as a significant prognostic factor for long-term survival in breast cancer. Our data also showed a role for Nrp2 in regulating cytoplasmic CXCR4 expression in vitro.

Show MeSH

Related in: MedlinePlus

Neuropilin-2 (Nrp2) expression in normal breast and breast carcinoma tissue. (A) Nrp2 staining was observed in blood or lymph vessels. There was no staining in normal breast epithelium. (×100). (B) In cancer tissue, staining of the Nrp2 protein was identified not only in the vascular endothelial cells, but also in the cytoplasm of cancer cells. Almost all invasive cells were immunopositive for Nrp2. (×200). (C-D) Co-localized expression of Nrp2 (C) and CXCR4 (D) using serial sections of breast carcinoma tissue. (×100).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2719661&req=5

Figure 1: Neuropilin-2 (Nrp2) expression in normal breast and breast carcinoma tissue. (A) Nrp2 staining was observed in blood or lymph vessels. There was no staining in normal breast epithelium. (×100). (B) In cancer tissue, staining of the Nrp2 protein was identified not only in the vascular endothelial cells, but also in the cytoplasm of cancer cells. Almost all invasive cells were immunopositive for Nrp2. (×200). (C-D) Co-localized expression of Nrp2 (C) and CXCR4 (D) using serial sections of breast carcinoma tissue. (×100).

Mentions: In normal breast tissue (Figure 1A), Nrp2 staining was observed in blood or lymph vessels, while there was no staining in normal breast epithelium. In cancer tissue, staining of the Nrp2 protein was identified not only in the vascular endothelial cells, but also in the cytoplasm of cancer cells. In some cases, almost all invasive cells were immunopositive for Nrp2 (Figure 1B). Nrp2 expression was identified in both marginal and central areas of the tumor. According to the criteria for Nrp2 immunostaining evaluation, Nrp2 protein was positive in 53.1% (60 of 113) of the invasive breast carcinomas.


Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression.

Yasuoka H, Kodama R, Tsujimoto M, Yoshidome K, Akamatsu H, Nakahara M, Inagaki M, Sanke T, Nakamura Y - BMC Cancer (2009)

Neuropilin-2 (Nrp2) expression in normal breast and breast carcinoma tissue. (A) Nrp2 staining was observed in blood or lymph vessels. There was no staining in normal breast epithelium. (×100). (B) In cancer tissue, staining of the Nrp2 protein was identified not only in the vascular endothelial cells, but also in the cytoplasm of cancer cells. Almost all invasive cells were immunopositive for Nrp2. (×200). (C-D) Co-localized expression of Nrp2 (C) and CXCR4 (D) using serial sections of breast carcinoma tissue. (×100).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2719661&req=5

Figure 1: Neuropilin-2 (Nrp2) expression in normal breast and breast carcinoma tissue. (A) Nrp2 staining was observed in blood or lymph vessels. There was no staining in normal breast epithelium. (×100). (B) In cancer tissue, staining of the Nrp2 protein was identified not only in the vascular endothelial cells, but also in the cytoplasm of cancer cells. Almost all invasive cells were immunopositive for Nrp2. (×200). (C-D) Co-localized expression of Nrp2 (C) and CXCR4 (D) using serial sections of breast carcinoma tissue. (×100).
Mentions: In normal breast tissue (Figure 1A), Nrp2 staining was observed in blood or lymph vessels, while there was no staining in normal breast epithelium. In cancer tissue, staining of the Nrp2 protein was identified not only in the vascular endothelial cells, but also in the cytoplasm of cancer cells. In some cases, almost all invasive cells were immunopositive for Nrp2 (Figure 1B). Nrp2 expression was identified in both marginal and central areas of the tumor. According to the criteria for Nrp2 immunostaining evaluation, Nrp2 protein was positive in 53.1% (60 of 113) of the invasive breast carcinomas.

Bottom Line: Survival curves determined by the Kaplan-Meier method showed that Nrp2 expression was associated with reduced overall survival.In multivariate analysis, Nrp2 expression emerged as a significant independent predictor for overall survival.Nrp2 expression may serve as a significant prognostic factor for long-term survival in breast cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Laboratory Medicine, Wakayama Medical University, Wakayama, Japan. hyasuoka@mail.wakayama-med.ac.jp

ABSTRACT

Background: Neuropilin-2 (Nrp2) is a receptor for vascular endothelial growth factor-C (VEGF-C), which is a well-known lymphangiogenic factor and plays an important role in lymph node metastasis of various human cancers, including breast cancer. Recently, Nrp2 was shown to play a role in cancer by promoting tumor cell metastasis. CXC chemokine receptor 4 (CXCR4) also promotes tumor metastasis. In the previous studies, we demonstrated that VEGF-C and cytoplasmic CXCR4 expressions were correlated with poorer patient prognosis (BMC Cancer 2008,8:340; Breast Cancer Res Treat 2005, 91:125-132).

Methods: The relationship between Nrp2 expression and lymph node metastasis, VEGF-C expression, CXCR4 expression, and other established clinicopathological variables (these data were cited in our previous papers), including prognosis, was analyzed in human breast cancer. Effects of neutralizing anti-Nrp2 antibody on CXCR4 expression and chemotaxis were assessed in MDA-MB-231 breast cancer cells.

Results: Nrp2 expression was observed in 53.1% (60 of 113) of the invasive breast carcinomas. Nrp2 expression was significantly correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Survival curves determined by the Kaplan-Meier method showed that Nrp2 expression was associated with reduced overall survival. In multivariate analysis, Nrp2 expression emerged as a significant independent predictor for overall survival. Neutralizing anti-Nrp2 antibody blocks cytoplasmic CXCR4 expression and CXCR4-induced migration in MDA-MB-231 cells.

Conclusion: Nrp2 expression was correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Nrp2 expression may serve as a significant prognostic factor for long-term survival in breast cancer. Our data also showed a role for Nrp2 in regulating cytoplasmic CXCR4 expression in vitro.

Show MeSH
Related in: MedlinePlus