Abstract
BackgroundPatients with ovarian cancer commonly have a poor prognosis, owing to its invasiveness and distant metastasis. Studies have found TM4SF1 participates in regulating tumor cell invasion and migration. Therefore, it is expected to become a target for anti-invasion and metastasis in ovarian cancer.MethodsThe expression of TM4SF1 in normal ovarian epithelial tissues, benign ovarian tumor tissues, primary foci of epithelial ovarian cancer and the matched lymph mode metastatic foci was detected using immunohistochemistry to analyze its association with prognosis. The expression of TM4SF1 in HO8910PM, SKOV3 was inhibited using RNAi, and the growth, proliferation, migration, invasion abilities of HO8910PM and SKOV3 cells and the growth of xenograft tumors in nude mice were examined.Results(1) The positive expression rate of TM4SF1 protein in epithelial ovarian cancer tissues (90.90%) was higher than that in benign ovarian tumor tissues (65.22%) and normal ovarian epithelial tissues (31.25%), and both differences were significant (P < 0.05). The expression of TM4SF1 protein was positive in all metastatic lymph node foci and matched primary foci (100%). (2) The level of TM4SF1 protein expression was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and histological grade. However, The positive TM4SF1 protein expression was not an independent factor of prognosis (P > 0.05). (3) Silencing TM4SF1 expression did not affect growth, proliferation, or cell cycle distribution but inhibited the migration and invasion abilities of HO8910PM and SKOV3 cells. Silencing TM4SF1 expression inhibited the growth of xenograft tumors in nude mice.ConclusionTM4SF1 is a potential target for anti-invasion and metastasis in ovarian cancer.
Highlights
Patients with ovarian cancer commonly have a poor prognosis, owing to its invasiveness and distant metastasis
transmembrane 4 superfamily 1 (TM4SF1) is a potential target for anti-invasion and metastasis in ovarian cancer
Our study group previously applied the strategy of a combination of improved serological analysis of recombinant cDNA expression libraries (SEREX) technology and suppression subtractive hybridization (SSH) technology to screen and obtain the ovarian cancer associated antigen, transmembrane 4 superfamily 1 (TM4SF1), from a cDNA library constructed from ascites cancer cells of ovarian cancer patients [1]; in addition, the autoantibody of TM4SF1 could be used for early diagnosis of ovarian cancer [2]
Summary
Patients with ovarian cancer commonly have a poor prognosis, owing to its invasiveness and distant metastasis. Studies have found TM4SF1 participates in regulating tumor cell invasion and migration. It is expected to become a target for anti-invasion and metastasis in ovarian cancer. Because early-stage ovarian cancer lacks typical clinical symptoms, approximately 2/3 of patients already have advanced stage cancer upon clinical diagnosis. Among these patients, approximately 2/3 die of tumor recurrence and metastasis within 5 years. Several studies have already confirmed that high TM4SF1 expression in various epithelial malignant tumors can regulate cancer cell invasion and metastasis and is associated with poor prognosis [3,4,5,6].
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