The Number Of Polyploid Giant Cancer Cells And Epithelial Mesenchymal Transition-related Proteins Are Associated With Invasion And Metastasis In Human Breast Cancer

Background:Previously, we reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride (CoCl2) could have generated daughter cells with strong invasiveness and migration capabilities via asymmetric divisions. This study compared the expression of epithelial-mesenchymal transition (EMT)-related proteins, including E-cadherin, N-cadherin, and vimentin, between PGCCs and their daughter cells, derived from MCF-7 and MDA-MB-231 respectively, and the coreesponding control breast cancer cell lines MCF-7 and MDA-MB-231. The clinicopathological significance of EMT-related protein expression and PGCCs numbers in human breast cancer was analyzed.Methods:Firstly, western blot was used to compare the expression levels of E-cadherin, N-cadherin, and vimentin in breast cancer lines MCF-7 and MDA-MB-231, between PGCCs with budding daughter cells and control breast cancer cells. Meanwhile, the wound-healing assay and transwell assay were used to compare the migration and invasion ability between PGCCs with budding daughter cells and control breast cancer cells. Secondly, paraffin-embedded tissue samples of 104 cases of breast cancer and 11 cases of benign breast tumor (fibroadenoma) were collected, including samples obtained from 52 patients with primary breast carcinoma with lymph node metastasis (group I) and their corresponding lymph node metastatic tumors (group II),52 patients with primary breast carcinoma without lymph node metastasis (group III), and 11 patients with benign breast lesions (group IV). The expression of E-cadherin, N-cadherin, and vimentin was detected and the numbers of PGCCs were counted among these four groups.Results:Firstly, compared with control cells, western blot analysis revealed that E-cadherin expression was lower in PGCCs with budding and that expression of N-cadherin and vimentin was greater in PGCCs with budding which had the stronger ability of migration and invasion. Secondly, the expression level of E-cadherin (p= 0.000) was decreasing in the order of benign breast lesions (group IV), primary breast carcinoma without lymph node metastasis (group III), primary breast carcinoma with lymph node metastasis (group I) and lymph node metastatic tumors (group â…¡). Meanwhile, expression levels of N-cadherin (p=0.000) and vimentin (p=0.000) were increasing in sequenceas the above-mentioned four groups. In addition, the numbers of PGCCs (p=0.000) among the above-mentioned four groups were also increasing in sequence. Both the expression levels of E-cadherin, N-cadherin, and vimentin and the number of PGCCs among the four groups were statistically different.Conclusions:These data suggest that the number of PGCCs and the expression of EMT-related proteins E-cadherin, N-cadherin and vimentin may be valuable and potential biomarkers to assess lymph node metastasis in patients with breast cancer.