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Overexpression of semaphorin 3A promotes tumor progression and predicts poor prognosis in hepatocellular carcinoma after curative resection.
- Source :
-
Oncotarget [Oncotarget] 2016 Aug 09; Vol. 7 (32), pp. 51733-51746. - Publication Year :
- 2016
-
Abstract
- The semaphorins were originally identified as having roles as guidance cues during neural development. Class 3 semaphorins are involved in cancer progression. However, the roles of class 3 semaphorins in hepatocellular carcinoma (HCC) are unknown. We examined the expression levels of class 3 semaphorins in HCC cell lines with different metastatic potential and in carcinoma tissue samples. The results indicated that Semaphorin 3A expression was up-regulated in metastatic cell lines and in samples from patients with tumor recurrence. Cell functional studies revealed that Semaphorin 3A promoted HCC cell proliferation, migration, and invasion. Animal studies indicated that Semaphorin 3A overexpression enhanced tumor growth and lung metastasis. Semaphorin 3A also acted as a chemoattractant involved in direct recruitment of macrophages in vitro, and facilitated tumor-associated macrophage (TAM) infiltration in vivo. Multivariate analysis revealed that Semaphorin 3A expression alone, or combined with the number of TAMs, can be an independent predictor for overall survival time and time to recurrence. Overall, the results suggested that Semaphorin 3A increased TAM infiltration and promoted HCC progression. Semaphorin 3A expression alone, or combined with the number of TAMs, is a new prognostic factor and potential target for the treatment of HCC.<br />Competing Interests: The authors disclose no conflicts.
- Subjects :
- Adult
Aged
Aged, 80 and over
Animals
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular mortality
Cell Line, Tumor
Cohort Studies
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Hepatectomy
Humans
Liver Neoplasms genetics
Liver Neoplasms mortality
Macrophages metabolism
Macrophages pathology
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Prognosis
Up-Regulation
Carcinoma, Hepatocellular diagnosis
Carcinoma, Hepatocellular surgery
Liver Neoplasms diagnosis
Liver Neoplasms surgery
Semaphorin-3A genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27351132
- Full Text :
- https://doi.org/10.18632/oncotarget.10104