Tumor-derived microvesicles are rich in metastasis-related proteases and play a role in the interactions between tumor cells and tumor microenvironment in tumor metastasis. Because shed microvesicles may remain in the extracellular environment around tumor cells, the microvesicle membrane protein may be the potential target for cancer therapy. Here we report that chromosome segregation 1-like (CSE1L) protein is a microvesicle membrane protein and is a potential target for cancer therapy. v-H-Ras expression induced extracellular signal-regulated kinase (ERK)-dependent CSE1L phosphorylation and microvesicle biogenesis in various cancer cells. CSE1L overexpression also triggered microvesicle generation, and CSE1L knockdown diminished v-H-Ras-induced microvesicle generation, matrix metalloproteinase (MMP)-2 and MMP-9 secretion and metastasis of B16F10 melanoma cells. CSE1L was preferentially accumulated in microvesicles and was located in the microvesicle membrane. Furthermore, anti-CSE1L antibody-conjugated quantum dots could target tumors in animal models. Our findings highlight a novel role of Ras-ERK signaling in tumor progression and suggest that CSE1L may be involved in the "early" and "late" metastasis of tumor cells in tumorigenesis. Furthermore, the novel microvesicle membrane protein, CSE1L, may have clinical utility in cancer diagnosis and targeted cancer therapy.

No abstract

RU486 is antagonistic to the rapid mPR-mediated non-genomic responses, but is synergistic with progesterone with respect to the inhibition of PHA-induced cell proliferation. Our findings shine new light on RU486's clinical application and how this relates to the non-genomic rapid physiological responses caused by progesterone.

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.

BackgroundColorectal carcinomas spread easily to nearby tissues around the colon or rectum, and display strong potential for invasion and metastasis. CSE1L, the chromosome segregation 1-like protein, is implicated in cancer progression and is located in both the cytoplasm and nuclei of tumor cells. We investigated the prognostic significance of cytoplasmic vs. nuclear CSE1L expression in colorectal cancer.MethodsThe invasion- and metastasis-stimulating activities of CSE1L were studied by in vitro invasion and animal experiments. CSE1L expression in colorectal cancer was assayed by immunohistochemistry, with tissue microarray consisting of 128 surgically resected specimens; and scored using a semiquantitative method. The correlations between CSE1L expression and clinicopathological parameters were analyzed.ResultsCSE1L overexpression was associated with increased invasiveness and metastasis of cancer cells. Non-neoplastic colorectal glands showed minimal CSE1L staining, whereas most colorectal carcinomas (99.2%, 127/128) were significantly positive for CSE1L staining. Cytoplasmic CSE1L was associated with cancer stage (P=0.003) and depth of tumor penetration (P=0.007). Cytoplasmic CSE1L expression also correlated with lymph node metastasis of the disease in Cox regression analysisConclusionsCSE1L regulates the invasiveness and metastasis of cancer cells, and immunohistochemical analysis of cytoplasmic CSE1L in colorectal tumors may provide a useful aid to prognosis.