Abstract P2-01-20: LAP2alpha, a novel tumor marker candidate is related to metastasis of breast cancer

Abstract

Abstract Background: To date, there is no suitable serum marker for diagnosis and prognosis of breast cancer. In our early research, a new tumor marker candidate of breast cancer whose molecular weight was 5.6 kDa was screened from serum using mass spectrometry technology. It was decoded to be a fragment of isoform alpha of lamina-associated polypeptide 2 (LAP2α). The survival analysis revealed that LAP2α was over-expressed in breast cancer patients and indicated poor prognosis. Materials and Methods: Immunohistochemistry (IHC) was utilized to evaluate LAP2α expression in paired primary breast tumor, metastasis of axillary lymph node and ipsilateral normal breast tissue of 29 breast cancer patients. An inhibition plasmid vector of LAP2α-small hairpin RNA (LAP2α-shRNA) was constructed and transfected into MCF-7 cells. The abilities of cell proliferation and metastasis were assessed both in vitro and in vivo. The association of LAP2α with epithelial-to-mesenchymal transition (EMT) was determined by western blot. Results: LAP2α expression of paired tissue descended in order of metastasis of axillary lymph node (21/29, 72.4%), primary breast tumor (11/29, 37.9%) and ipsilateral normal breast tissue (4/29, 13.8%) (P<0.05 in comparisons between each two groups). CCK-8 experiments on transfected and control cells showed that inhibition of LAP2α could not influence cell proliferation. Transwell and matrigel-transwell assays indicated that inhibition of LAP2α could significantly reduce cell migration and invasion abilities. In vivo experiments utilizing subcutaneous xenograft model and tail vein-injection mouse model revealed that the down-regulation of LAP2α might suppress tumorigenesis and metastasis of breast cancer. Western blot suggested that down regulation of LAP2α increased the E-cadherin expression level but repressed N-cadherin and vimentin expression levels. Conclusions: A novel tumor marker candidate, LAP2α is related to metastasis of breast cancer both in clinical samples and tissue culture experiments. Inhibition of LAP2α could suppress aggressiveness and metastasis of breast cancer probably via EMT suppression. Funding: The Natural Science Foundation of Zhejiang Province of China (No. LY14H160030 and LY13H160011), the National Program on Key Basic Research Project of China (973 Program; No. 2014CB542003), the National Natural Science Foundation of China (No. 30801341) and Zheng Shu Elite Scholarship for Clinical Medicine. Citation Format: Hu Y, Qiu J, Zhou M, Li X, Huang Y. LAP2alpha, a novel tumor marker candidate is related to metastasis of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-20.