Deficiency of Follistatin-Like Protein 1 Accelerates the Growth of Breast Cancer Cells at Lung Metastatic Sites / 한국유방암학회지

PURPOSE: Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has been shown to play a role in various types of cancer. However, the clinical significance and function of FSTL1 in breast cancer have not been reported. We investigated the role of FSTL1 in breast cancer in this study. METHODS: Enzyme-linked immunosorbent assays, western blot analysis, and reverse transcription polymerase chain reaction were used to monitor the expression of FSTL1 in breast cancer tissue and in serum samples from breast cancer patients. We employed a 4T1 breast cancer model and Fstl1(+/−) mice for in vivo studies. Hematoxylin and eosin staining, western blot analysis, and RNA sequencing were used to analyze the effect of FSTL1 on primary tumor growth and lung metastasis. RESULTS: We demonstrated that the expression of FSTL1 is reduced in both the breast cancer tissue and the serum of breast cancer patients. We showed that reduced levels of FSTL1 in serum correlate with elevated expression of Ki-67 and epidermal growth factor receptor (EGFR) in cancer tissues. Moreover, lowered expression of FSTL1 was associated with decreased survival in breast cancer patients. Experiments on the Fstl1(+/−) mouse model established that FSTL1 deficiency had no effect on primary tumor growth, but increased the lung metastases of breast cancer cells, resulting in reduced survival of tumor-bearing mice. RNA sequencing found significantly reduced expression of Egln3 and increased expression of EGFR in Fstl1(+/−) mice. Thus, our results suggest that FSTL1 may affect the expression of EGFR through Egln3, inhibiting the proliferation of breast cancer cells at lung metastatic sites. CONCLUSION: In conclusion, we suggest a suppressor role of FSTL1 in breast cancer lung metastasis. Furthermore, FSTL1 may represent a potential prognostic biomarker and a candidate therapeutic target in breast cancer patients.

Expression of follistatin-like protein 1 in the peripheral blood and intestinal tissue of patients with ulcerative colitis and its clinical significance / 中华消化杂志

Objective To examine the expression of follistatin-like protein 1 (FSTL1) in the peripheral blood and intestinal mucosa tissues of ulcerative colitis (UC) patients and analyze the correlation between its expression and the activity of UC.Methods From October 2010 to June 2012,sixty patients with UC were collected.From April 2012 to October 2012,thirty individuals without any obvious mucosa lesion under colonoscope and confirmed by pathological examination were set as control group.The serum expression level of FSTL1 of both UC group and control group were determined by enzyme linked immunosorbent assay (ELISA).t-test was performed for comparison between groups.The expression of FSTL1 in the intestinal mucosa of UC group and control group was detected by immunohistochemistry.Chi-square test was used for comparison between groups.The patients with UC were scored with ulcerative colitis disease activity index (UCDAI).Its correlation with plasma FSTL1 was analyzed by Pearson correlation coefficient.Results The serum expression level of FSTL1 of UC group ((14.37-±-1.80) μg/L) was higher than that of control group ((5.80±0.72) μg/L)and the difference was statistically significant (t=25.01,P＜ 0.05).The serum expression level of FSTL1 of UC group was positively correlated with UCDAI (r=0.814,P＜0.05).The positive expression rate of FSTL1 in the intestinal mucosa tissues of UC group (86.7％,52/60)was higher than that of control group (46.7％,14/30) and the difference was statistically significant (x2 =52.334,P＜0.05).Conclusions The expression of FSTL1 of UC patients increases and is positively correlated with disease activity.FSTL1 may play a role in the development of UC.