Abstract
Over-expression of Crk-like protein (CrkL), an intracellular adaptor protein, in breast cancer biopsies has been linked to poor prognosis. CrkL can be secreted from cancer cells binding to β1 integrin on the cell membrane. In this study, we evaluated, for the first time, the levels of soluble CrkL in serum of breast cancer patients. Expression of CrkL and secreted fractions from human breast cancer cell lines and clinical patient samples were assessed by immunohistochemistry and Enzyme Linked Immuno-Sorbent Assay (ELISA). CrkL levels in tissues and sera of patients with different disease stages were compared and statistically analyzed by Chi-square test and Student’s t-test. Culture media from human breast cancer cell lines SUM159, MDA-MB231, and MCF7 showed over a 21-, 15-, and 11-fold higher concentration of soluble CrkL as compared to normal breast epithelium cell line MCF10A. Expression of CrkL was elevated in 85% of breast tumor tissue sections. Serum levels of CrkL were significantly higher in breast cancer patients than in healthy donors. All patients with metastatic disease had significantly elevated concentration of soluble CrkL in the serum with on average three-fold increase from the baseline. The data suggest that soluble fraction of CrkL can be further evaluated as a serum biomarker for advanced disease in breast cancer patients.
Highlights
Initiation and progression of many ailments causes changes in the level of expression of proteins involved in the pathologic course of the disease [1]
Proteins that are over-expressed on the cancer cells and in the tumor microenvironment (TME), as well as proteins secreted from the tumors and detected in the patient’s fluids, can be collected and, have been and are being used in the clinic as markers for tumor prognosis and diagnosis [2]
To assess the secreted fraction of Crk-like protein (CrkL) bound to the cell membrane, a flow cytometry analysis was conducted on three non-permeabilized breast cancer cell lines, as compared to the normal breast epithelium cell line
Summary
Initiation and progression of many ailments causes changes in the level of expression of proteins involved in the pathologic course of the disease [1]. Proteins that are over-expressed on the cancer cells and in the tumor microenvironment (TME), as well as proteins secreted from the tumors and detected in the patient’s fluids, can be collected and, have been and are being used in the clinic as markers for tumor prognosis and diagnosis [2]. Used soluble markers for cancer diagnosis include mesothelin in malignant pleural mesothelioma [3], colony stimulating factor-1 (CSF-1) [4] for endometrial carcinoma, prostate specific antigen (PSA) for prostate cancer [5], and carcinoembryonic antigen, CA125, for ovarian cancer [6]. A number of plasma biomarkers, such as vascular endothelial growth factor (VEGF) and carcinoembryonic antigens, CA 15.3 and CA 27.59, were found to have a prognostic value [7]. While the knowledge about existing biomarkers is growing, it is important to find new possible biomarkers that can complement the existing panel for providing a better disease diagnosis and prognosis
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