TM4SF1 is a potential target for anti-invasion and metastasis in ovarian cancer

Caiyun Gao, Hongyu Yao, Huimin Liu, Yanying Feng, Zhijun Yang, Caiyun Gao, Hongyu Yao, Huimin Liu, Yanying Feng, Zhijun Yang

Abstract

Background: 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. Therefore, it is expected to become a target for anti-invasion and metastasis in ovarian cancer.

Methods: The 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.

Conclusion: TM4SF1 is a potential target for anti-invasion and metastasis in ovarian cancer.

Keywords: Invasion; Metastasis; Ovarian cancer; TM4SF1; Target.

Conflict of interest statement

Ethics approval and consent to participate

The use of patients’ tissues and data for the study had obtained written consents from all participates. The study was approved by The Ethics Committee of Affiliated tumor hospital of Guangxi Medical University with the following reference number: NO. LW2018001, and the research were conducted in conformity with the Declaration of Helsinki and the NIH guidelines (NIH Pub. No. 85–23, revised 1996) .

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
TM4FS1 expression in ovarian tissues and metastatic lymph node foci detected by IHC (400X). a Positive control. b Negative expression of normal ovarian epithelial tissues. c Positive expression of normal ovarian epithelial tissues. d Positive expression of ovarian benign tumor tissues. e Positive expression of epithelial ovarian cancer tissues. f Positive expression of metastatic lymph node foci. Black arrows: Expression of TM4FS1 is concentrated in the membrane or near the basement membrane of the cell membrane; Red arrows: Expression of TM4FS1 is concentrated in the cytoplasm
Fig. 2
Fig. 2
Expression of TM4SF1 in HO8910PM and SKOV3 cells after RNAi. a Expression of TM4SF1 interfered by different siRNAs. b, d Expression of TM4SF1 gene and protein in HO8910 after RNAi. c, e Expression of TM4SF1 gene and protein in SKOV3 cells after RNAi. *: p < 0.05 (Fig. 2a: * compared with control)
Fig. 3
Fig. 3
The effect of RNAi on the growth of HO8910PM and SKOV3 cells. a Knockdown of TM4SF1 did not affect HO8910PM cells growth. b Knockdown of TM4SF1 did not affect and SKOV3 growth
Fig. 4
Fig. 4
The effect of RNAi on cell cycle of HO8910PM and SKOV3 cells. a Cell cycle of LV-CON-RNAi-Luc/HO8910PM cells. b Cell cycle of LV-TM4SF1-RNAi-Luc/HO8910PM. c Cell cycle of LV-CON-RNAi-Luc/SKOV3 cells. d Cell cycle of LV-TM4SF1-RNAi-Luc/SKOV3 cells
Fig. 5
Fig. 5
The effect of RNAi on the colony formation, migration, invasion abilities of HO8910PM and SKOV3 cells. a Knockdown of TM4SF1 did not affect HO8910PM cells colony formation. b Knockdown of TM4SF1 inhibited HO8910PM cells migration. c Knockdown of TM4SF1 inhibited HO8910PM cells invasion. d Knockdown of TM4SF1 did not affect SKOV3 cells colony formation. e Knockdown of TM4SF1 inhibited SKOV3 cells migration. f Knockdown of TM4SF1 inhibited SKOV3 cells invasion. *p < 0.05, **p < 0.001
Fig. 6
Fig. 6
The growth of xenograft tumor inhibited by RNAi. a, c Volume of xenograft tumor. b luminescence signal of xenograft tumor detected by live imaging system. d Expression of TM4SF1 gene in xenograft tumor. e Expression of TM4SF1 protein in xenograft tumor

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