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Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion.

Roselli S, Pundavela J, Demont Y, Faulkner S, Keene S, Attia J, Jiang CC, Zhang XD, Walker MM, Hondermarck H - Oncotarget (2015)

Bottom Line: It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001).Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation.In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.

ABSTRACT
The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion.

No MeSH data available.


Related in: MedlinePlus

Frequency distribution of sortilin levelsSortilin levels (0 = no staining, 1 = low intensity staining, 2 = intermediate intensity staining, 3 = high intensity staining) were measured in breast cancers and normal breast tissues. A. Distribution in normal tissues versus breast tumors. B. Distribution in invasive lobular carcinomas (ILC) versus invasive ductal carcinomas (IDC). C. Distribution in lymph node negative (LN-) versus lymph node positive (LN+) cancers. Number of cases (n) is indicated. Statistical significance of the difference between groups are reported in Table 1.
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Figure 2: Frequency distribution of sortilin levelsSortilin levels (0 = no staining, 1 = low intensity staining, 2 = intermediate intensity staining, 3 = high intensity staining) were measured in breast cancers and normal breast tissues. A. Distribution in normal tissues versus breast tumors. B. Distribution in invasive lobular carcinomas (ILC) versus invasive ductal carcinomas (IDC). C. Distribution in lymph node negative (LN-) versus lymph node positive (LN+) cancers. Number of cases (n) is indicated. Statistical significance of the difference between groups are reported in Table 1.

Mentions: Sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 adjacent normal tissues. Sortilin expression was found only in epithelial cells of both normal and cancerous samples (Fig. 1). No labeling was observed in the stroma: fibroblasts, endothelial cells, adipocytes and extracellular matrix were all negative. The frequency distribution of sortilin levels (Fig. 2) showed that the majority of normal tissues had low levels of sortilin (staining intensity 0 and 1), while the proportion of cases with intermediate (staining intensity 2) and high (staining intensity 3) levels of sortilin increased in cancers and in particular in invasive ductal carcinomas (IDC) and lymph node positive tumors. There was a clear difference between sortilin positive and sortilin negative cases (Fig. 1) and among sortilin positive cases, the staining intensities were fairly homogeneous (mostly staining intensities 1 and 2). Therefore, the data were expressed in terms of sortilin positive versus sortilin negative cancer cases (Table 1). Analysis of relationships between sortilin expression and clinicopathological parameters revealed sortilin expression in 66% of breast cancers compared to 47% of adjacent normal tissues (p = 0.0088). A difference in expression between invasive ductal carcinomas (IDC) and invasive lobular carcinomas (ILC) was observed: 79% of IDC were positive for sortilin as compared to 54% of ILC (p < 0.0001). No significant association of sortilin expression was observed with tumor size, grade, patient age, ER and PR, and molecular subtypes of breast cancer (luminal A and B, HER2+, triple negative). Sortilin was expressed in 59% of triple negative breast cancers. In addition, there was a trend toward more tumors expressing sortilin among HER2-positive tumors (77%) than among HER2-negative tumors (63%) but the p-value was limited (p = 0.0349). A significant association was found between sortilin expression and lymph node invasion. Sortilin was expressed in 60% of lymph node negative cancers versus 75% of lymph node positive cancers (p = 0.0093), suggesting a positive relationship between sortilin expression and the metastatic potential. In Log-Linear modeling, two-way analyses confirmed the association, adjusted for all other variables, of sortilin with histological type (ductal vs. lobular invasive carcinomas, p = 0.002) and lymph node invasion (OR = 1.55 for lymph node positivity, p = 0.096).


Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion.

Roselli S, Pundavela J, Demont Y, Faulkner S, Keene S, Attia J, Jiang CC, Zhang XD, Walker MM, Hondermarck H - Oncotarget (2015)

Frequency distribution of sortilin levelsSortilin levels (0 = no staining, 1 = low intensity staining, 2 = intermediate intensity staining, 3 = high intensity staining) were measured in breast cancers and normal breast tissues. A. Distribution in normal tissues versus breast tumors. B. Distribution in invasive lobular carcinomas (ILC) versus invasive ductal carcinomas (IDC). C. Distribution in lymph node negative (LN-) versus lymph node positive (LN+) cancers. Number of cases (n) is indicated. Statistical significance of the difference between groups are reported in Table 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496368&req=5

Figure 2: Frequency distribution of sortilin levelsSortilin levels (0 = no staining, 1 = low intensity staining, 2 = intermediate intensity staining, 3 = high intensity staining) were measured in breast cancers and normal breast tissues. A. Distribution in normal tissues versus breast tumors. B. Distribution in invasive lobular carcinomas (ILC) versus invasive ductal carcinomas (IDC). C. Distribution in lymph node negative (LN-) versus lymph node positive (LN+) cancers. Number of cases (n) is indicated. Statistical significance of the difference between groups are reported in Table 1.
Mentions: Sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 adjacent normal tissues. Sortilin expression was found only in epithelial cells of both normal and cancerous samples (Fig. 1). No labeling was observed in the stroma: fibroblasts, endothelial cells, adipocytes and extracellular matrix were all negative. The frequency distribution of sortilin levels (Fig. 2) showed that the majority of normal tissues had low levels of sortilin (staining intensity 0 and 1), while the proportion of cases with intermediate (staining intensity 2) and high (staining intensity 3) levels of sortilin increased in cancers and in particular in invasive ductal carcinomas (IDC) and lymph node positive tumors. There was a clear difference between sortilin positive and sortilin negative cases (Fig. 1) and among sortilin positive cases, the staining intensities were fairly homogeneous (mostly staining intensities 1 and 2). Therefore, the data were expressed in terms of sortilin positive versus sortilin negative cancer cases (Table 1). Analysis of relationships between sortilin expression and clinicopathological parameters revealed sortilin expression in 66% of breast cancers compared to 47% of adjacent normal tissues (p = 0.0088). A difference in expression between invasive ductal carcinomas (IDC) and invasive lobular carcinomas (ILC) was observed: 79% of IDC were positive for sortilin as compared to 54% of ILC (p < 0.0001). No significant association of sortilin expression was observed with tumor size, grade, patient age, ER and PR, and molecular subtypes of breast cancer (luminal A and B, HER2+, triple negative). Sortilin was expressed in 59% of triple negative breast cancers. In addition, there was a trend toward more tumors expressing sortilin among HER2-positive tumors (77%) than among HER2-negative tumors (63%) but the p-value was limited (p = 0.0349). A significant association was found between sortilin expression and lymph node invasion. Sortilin was expressed in 60% of lymph node negative cancers versus 75% of lymph node positive cancers (p = 0.0093), suggesting a positive relationship between sortilin expression and the metastatic potential. In Log-Linear modeling, two-way analyses confirmed the association, adjusted for all other variables, of sortilin with histological type (ductal vs. lobular invasive carcinomas, p = 0.002) and lymph node invasion (OR = 1.55 for lymph node positivity, p = 0.096).

Bottom Line: It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001).Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation.In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.

ABSTRACT
The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion.

No MeSH data available.


Related in: MedlinePlus