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Detecting the Role of CCR7-CCL21/CCL19 Axis in Breast Cancer Progression and Lymph Node Metastasis Incidence


Affiliations
1 Department of Biochemistry and Microbiology, Tishreen University, Lattakia, Syrian Arab Republic
2 Department of Pathology, Tishreen University, Lattakia, Syrian Arab Republic
     

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Background: Metastasis is the main cause of death in breast cancer patients. Lymph node metastasis is associated with poor overall survival and is often associated with recurrences. The molecular mechanisms controlling tumor metastasis are complex and there is an emerging evidence supporting the direct involvement of the chemokines and their receptors in this process. To the interest of this study, previous data from the literature show that the CCL21 and CCL19 and their receptor CCR7 are expressed in breast cancer and may be associated with lymph node metastasis. The aim of this study is to assess the expression of CCL19/CCL21 and their receptor CCR7 in breast cancer tissues and both negative and positive regional lymph nodes using RT-PCR technology .

Material and Methods: Formalin fixed paraffin embedded breast cancer specimens obtained from mastectomy were included in the study. RNA isolation using Acidic Phenol method was performed, and then RT-PCR was conducted on both primary tumor and corresponding lymph nodes using specific primers for the studied CCL21/CCL19 chemokines, CCR7 receptor and the positive control GAPDH.

Results: The results of this study have revealed a significant positive correlation in mRNA expression in the tumor samples between CCL21 vs.CCL19 (R2=0.9,P-value= 0.02), as well as between CCR7 vs CCL21, and CCR7vs.CCL19 (R2=0.87, P value= 0.04) (R2=0.98,P value= 0.002) respectively. Moreover, there was a significant positive correlation (R2=0.9 , P value= 0.02) in CCL19 expression in primary and secondary tumor. Furthermore, the expression of CCL21 chemokine in negative lymph nodes was more than the expression of it in positive lymph nodes with significant importance (P value = 0.01). The Study of the correlation between CCL21/CCL19 expression in breast tumors and the clinical and pathological parameters, has illustrated a significant correlation between CCL21 vs. CCL19 mRNA expression in breast tumors and triple negative of PR, ER, Her-2 receptors.

Conclusion: The results of the study have revealed a potential role of CCR7-CCL21/CCL19 axis in breast cancer. Moreover the results suggest an important role of CCL19 in Lymph nodes metastasis compared to CCL21. Furthermore, the study has showed that CCL21/CCL19 chemokines are expressed in breast tumors with poor prognosis.


Keywords

Breast Cancer, Lymph Node Metastasis, CCR7, CCL19, CCL21.
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  • Detecting the Role of CCR7-CCL21/CCL19 Axis in Breast Cancer Progression and Lymph Node Metastasis Incidence

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Authors

Kenan Aloss
Department of Biochemistry and Microbiology, Tishreen University, Lattakia, Syrian Arab Republic
Sham Jdeed
Department of Biochemistry and Microbiology, Tishreen University, Lattakia, Syrian Arab Republic
Zuheir Alshehabi
Department of Pathology, Tishreen University, Lattakia, Syrian Arab Republic

Abstract


Background: Metastasis is the main cause of death in breast cancer patients. Lymph node metastasis is associated with poor overall survival and is often associated with recurrences. The molecular mechanisms controlling tumor metastasis are complex and there is an emerging evidence supporting the direct involvement of the chemokines and their receptors in this process. To the interest of this study, previous data from the literature show that the CCL21 and CCL19 and their receptor CCR7 are expressed in breast cancer and may be associated with lymph node metastasis. The aim of this study is to assess the expression of CCL19/CCL21 and their receptor CCR7 in breast cancer tissues and both negative and positive regional lymph nodes using RT-PCR technology .

Material and Methods: Formalin fixed paraffin embedded breast cancer specimens obtained from mastectomy were included in the study. RNA isolation using Acidic Phenol method was performed, and then RT-PCR was conducted on both primary tumor and corresponding lymph nodes using specific primers for the studied CCL21/CCL19 chemokines, CCR7 receptor and the positive control GAPDH.

Results: The results of this study have revealed a significant positive correlation in mRNA expression in the tumor samples between CCL21 vs.CCL19 (R2=0.9,P-value= 0.02), as well as between CCR7 vs CCL21, and CCR7vs.CCL19 (R2=0.87, P value= 0.04) (R2=0.98,P value= 0.002) respectively. Moreover, there was a significant positive correlation (R2=0.9 , P value= 0.02) in CCL19 expression in primary and secondary tumor. Furthermore, the expression of CCL21 chemokine in negative lymph nodes was more than the expression of it in positive lymph nodes with significant importance (P value = 0.01). The Study of the correlation between CCL21/CCL19 expression in breast tumors and the clinical and pathological parameters, has illustrated a significant correlation between CCL21 vs. CCL19 mRNA expression in breast tumors and triple negative of PR, ER, Her-2 receptors.

Conclusion: The results of the study have revealed a potential role of CCR7-CCL21/CCL19 axis in breast cancer. Moreover the results suggest an important role of CCL19 in Lymph nodes metastasis compared to CCL21. Furthermore, the study has showed that CCL21/CCL19 chemokines are expressed in breast tumors with poor prognosis.


Keywords


Breast Cancer, Lymph Node Metastasis, CCR7, CCL19, CCL21.

References