2919

CXCL1

chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha);CXCL1;chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)

C-X-C motif chemokine 1|GRO-alpha(1-73)|GRO1 oncogene (melanoma growth stimulating activity, alpha)|GRO1 oncogene (melanoma growth-stimulating activity)|MGSA alpha|fibroblast secretory protein|growth-regulated alpha protein|melanoma growth stimulatory act

4q21

protein-coding

The dietary antioxidant Curcumin has been proposed for cancer chemoprevention since it induces apoptosis and inhibits the formation of breast cancer metastases. Curcumin acts through the inhibition of phosphorylation of the inhibitor of kappa B (IkappaB), which in turn reduces the nuclear translocation of nuclear factor kappa B (NFkappaB), an inflammation- and cell survival-related transcription factor. However, it is not clear whether the strong antimetastatic effect can exclusively be explained by inhibition of NFkappaB. Here, we addressed the effects of Curcumin (IC(50) = 17 muM) in MDA-MB-231 breast cancer cells using microarray gene expression analyses. Among the 62 genes whose expression was significantly altered, we found the two inflammatory cytokines CXCL1 and -2 (Groalpha and -beta) that were downregulated. Further validation of the microarray results by quantitative real-time reverse transcription-polymerase chain reaction, western blots and enzyme-linked immunosorbent assay revealed that Curcumin impairs transcription of CXCL1 and -2 >24 h and reduces the corresponding proteins. Using small interfering RNA techniques, we elucidated the underlying molecular mechanism revealing that reduction of CXCL1 and -2 messenger RNA levels is NFkappaB dependent and requires intact IkappaBalpha expression. Moreover, CXCL1 and -2 silencing leads to downregulation of several metastasis-promoting genes among which we found the cytokine receptor CXCR4. We therefore suggest that the decrease of CXCL1 and -2 mediated by Curcumin is involved in the inhibition of metastasis.

metastasis and chemoresistance in cancer are linked phenomena, but the molecular basis for this link is unknown. We uncovered a network of paracrine signals between carcinoma, myeloid, and endothelial cells that drives both processes in breast cancer. cancer cells that overexpress CXCL1 and 2 by transcriptional hyperactivation or 4q21 amplification are primed for survival in metastatic sites. CXCL1/2 attract CD11b(+)Gr1(+) myeloid cells into the tumor, which produce chemokines including S100A8/9 that enhance cancer cell survival. Although chemotherapeutic agents kill cancer cells, these treatments trigger a parallel stromal reaction leading to TNF-alpha production by endothelial and other stromal cells. TNF-alpha via NF-kB heightens the CXCL1/2 expression in cancer cells, thus amplifying the CXCL1/2-S100A8/9 loop and causing chemoresistance. CXCR2 blockers break this cycle, augmenting the efficacy of chemotherapy against breast tumors and particularly against metastasis. This network of endothelial-carcinoma-myeloid signaling interactions provides a mechanism linking chemoresistance and metastasis, with opportunities for intervention.

Gastric cancer (GC) is a heterogeneous disease that is not well detected by current tumor markers. Identifying molecular markers that can predict the potential for tumor progression is important for appropriate individualized therapy. Using the cancer metastasis Research Center microarray database (17K cDNA microarray), we identified genes that were differentially expressed between 96 cancer and 98 normal gastric tissues using significant analysis of microarrays. From these, we selected genes that were overexpressed more than twofold in tumor tissues that encode secreted proteins. The selected genes were validated with ELISA using the sera of 96 GC patients and 48 healthy donors. Our first round of selection included 6510 genes that were differentially expressed between 96 cancer and 98 normal gastric tissues with a minimal false discovery rate of 0.005%. Out of those genes, we picked 386 that encoded secreted proteins based on the SOURCE database. Of these genes, we focused on 55 that were overexpressed more than twofold in GC compared to normal tissues. With Ingenuity pathway Analysis, we found 34 genes related to cancer. One in particular, chemokine growth-regulated oncogene 1, CXCL1, has been linked to cancer progression in various cancer types, but not yet to GC. Levels of CXCL1 in serum samples of GC patients were significantly higher compared with healthy donors (P < 0.05). Within GC patients, CXCL1 serum levels increased according to tumor stage and lymph node metastasis. The CXCL1 gene appears to be a candidate marker for GC progression.

OBJECTIVE: To investigate the correlation between expression of growth regulated oncogene 1 (GRO-1) and some clinical biological characteristics of laryngeal carcinoma. METHOD: expression of GRO-1 and VEGF(vascular endothelial growth factor) protein were investigated by means of immunohistochemistry in 60 laryngeal carcinoma tissues, GRO-1 was detected by RT-PCR in 30 laryngeal carcinoma tissues and 10 normal laryngeal tissues. RESULT: The result of RT-PCR showed that the expression of GRO-1 in squamous cell carcinoma of larynx tissues was higher than those in normal laryngeal tissues (P < 0.01). The result of Immunohistochemistry revealed that the expression of GRO-1 in squamous cell carcinoma of larynx with the metastasis of lymph nodes was higher than those without metastasis (P < 0.05). There was no significant relationship between GRO-1 protein expression and patients'tumor histological difference (P > 0.05). The expression of GRO-1 had no significant difference in age, sex, location and T classification (P > 0.05). There was positive correlation in staining intensity between GRO-1 and VEGF (P < 0.05). CONCLUSION: GRO-1 can promote tumor growth, metastasis by several mechanism,the effect of GRO-1 on angiogenesis are consistent with the distribution of VEGF.