Metastatic markers are highly useful diagnostic and prognostic indicators of cancer metastasis. Herein, we report that secretory CSE1L/CAS, a cellular apoptosis susceptibility protein, is a new marker for metastatic cancer. CAS was colocalized with matrix metalloproteinase-2 in vesicles surrounding the outside of MCF-7 cell membranes, and the COOH-terminal domain of CAS was associated with matrix metalloproteinase-2-containing vesicles. Immunohistochemical staining for CAS was positive in the stroma and gland lumens of human metastatic cancer tissues. CAS was also detected in conditioned medium from B16-F10 melanoma cells and more frequently in the sera of patients with metastatic cancer than in sera from patients with primary cancer. Specifically, the prevalence of serum CAS in serum samples from 146 patients was 58.2% (32 of 55), 32.0% (8 of 25), and 12.1% (8 of 66) for patients with metastatic, invasive, and primary cancers, respectively. Our results suggest that CAS is a secretory protein associated with cancer metastasis, which may have clinical utility in metastatic cancer screening and diagnosis.
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