Identification of VEGF-regulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis

Metastasis is the primary cause of death in patients with breast cancer. Overexpression of c-myc in humans correlates with metastases, but transgenic mice only show low rates of micrometastases. We have generated transgenic mice that overexpress both c-myc and vascular endothelial growth factor (VEGF) (Myc/VEGF) in the mammary gland, which develop high rates of pulmonary macrometastases. Gene expression profiling revealed a set of deregulated genes in Myc/VEGF tumors compared to Myc tumors associated with the increased metastatic phenotype. Cross-comparisons between this set of genes with a human breast cancer lung metastasis gene signature identified five common targets: tenascin-C(TNC), matrix metalloprotease-2, collagen-6-A1, mannosidase-alpha-1A and HLA-DPA1. Signaling blockade or knockdown of TNC in MDA-MB-435 cells resulted in a significant impairment of cell migration and anchorage-independent cell proliferation. Mice injected with clonal MDA-MB-435 cells with reduced expression of TNC demonstrated a significant decrease (P<0.05) in (1) primary tumor growth; (2) tumor relapse after surgical removal of the primary tumor and (3) incidence of lung metastasis. Our results demonstrate that VEGF induces complex alterations in tissue architecture and gene expression. The TNC signaling pathway plays an important role in mammary tumor growth and metastases, suggesting that TNC may be a relevant target for therapy against metastatic breast cancer

Childhood facial vitiligo: how intractable is it?

Background Following the recent elucidation of its pathogenic mechanisms involving reactive oxygen species, use of vitamins, folic acid and antioxidants as adjuvant therapy has been suggested. Objective To evaluate the long-term outcome of childhood facial vitiligo who were treated with nutritional education, vitamin E (a-tocopherol 100–400 IU/day), folic acid (1–2 mg/day) and multivitamin intake and antioxidant cosmetics as the mainstay of treatment as well as the conventional therapies including oral, topical and/or intralesional corticosteroid, topical macrolactam, Excimer laser and epidermal graft. Methods Medical data and photographs of 111 paediatric facial vitiligo patients who had been followed up for longer than 1 year from March 1, 2003 to June 30, 2013 were extracted from data warehouse of electric medical records. Photographic evaluation and final visual outcome assessment was performed. Result By investigators assessment, 9% of patients demonstrated no improvement regardless of treatment modality, whereas 91% showed improvement of lesions. Among the latter, 33.3% resulted in >75% improvement; 18% in 50%– 75% improvement; 26.1% in 25%–50% improvement; and 13.5% in <25% improvement. In the final visual outcome assessment, Looking excellent was seen in 42.3%; looking very good in 30.6%; looking good in 17.1%; looking fair in 9.0%; and looking bad in 0.9%. Conclusion Although childhood facial vitiligo is quite refractory to treatment, the long-term outcome of this condition is not dismal with conventional vitiligo therapy along with basic nutritional therapeutic regimen.OAIID:oai:osos.snu.ac.kr:snu2015-01/102/2008000790/8SEQ:8PERF_CD:SNU2015-01EVAL_ITEM_CD:102USER_ID:2008000790ADJUST_YN:NEMP_ID:A079501DEPT_CD:801CITE_RATE:3.105FILENAME:childhood vitiligo jeadv.pdfDEPT_NM:의학과SCOPUS_YN:YCONFIRM:

Identification of VEGF-regulated genes associated with increased lung metastatic potential: functional involvement of tenascin-C in tumor growth and lung metastasis

Metastasis is the primary cause of death in patients with breast cancer. Overexpression of c-myc in humans correlates with metastases, but transgenic mice only show low rates of micrometastases. We have generated transgenic mice that overexpress both c-myc and vascular endothelial growth factor (VEGF) (Myc/VEGF) in the mammary gland, which develop high rates of pulmonary macrometastases. Gene expression profiling revealed a set of deregulated genes in Myc/VEGF tumors compared to Myc tumors associated with the increased metastatic phenotype. Cross-comparisons between this set of genes with a human breast cancer lung metastasis gene signature identified five common targets: tenascin-C(TNC), matrix metalloprotease-2, collagen-6-A1, mannosidase-alpha-1A and HLA-DPA1. Signaling blockade or knockdown of TNC in MDA-MB-435 cells resulted in a significant impairment of cell migration and anchorage-independent cell proliferation. Mice injected with clonal MDA-MB-435 cells with reduced expression of TNC demonstrated a significant decrease (P<0.05) in (1) primary tumor growth; (2) tumor relapse after surgical removal of the primary tumor and (3) incidence of lung metastasis. Our results demonstrate that VEGF induces complex alterations in tissue architecture and gene expression. The TNC signaling pathway plays an important role in mammary tumor growth and metastases, suggesting that TNC may be a relevant target for therapy against metastatic breast cancer