Annexin A2 positively contributes to the malignant phenotype and secretion of IL‐6 in DU145 prostate cancer cells

Abstract

Several groups, including ours, have reported that annexin A2 (ANXA2) expression is reduced in most prostate cancer (CaP). More recently, however, we reported that ANXA2 is expressed in some high-grade tumors, but the biologic consequence of this is currently unknown. To elucidate the function of ANXA2 in CaP, we reduced its expression in DU145 cells using shRNA and tested the impact on characteristics of malignancy. Reduction of ANXA2 suppressed anchorage-dependent and -independent cell growth without affecting invasiveness. Interestingly, interleukin-6 (IL-6) secretion was reduced concomitantly with the reduction of ANXA2 but independently of S100A10. IL-6 expression was restored when wild type but not mutant ANXA2 was reexpressed in these cells. In a retrospective study of radical prostatectomy specimens from patients with nonmetastatic CaP, 100% of patients with ANXA2-positive tumors (n 5 4) had a biochemical relapse while only 50% of patients with ANXA2 negative tumors (n 5 20) relapsed, suggesting that ANXA2 expression in prostate tumors may be predictive of biochemical relapse. Significant cytoplasmic staining of ANXA2 was detected in 3 of 4 ANXA2-positive tumors, whereas ANXA2 is localized to the plasma membrane in benign prostatic glands. These finding, taken together, suggests a possible mechanism whereby ANXA2 expression positively contributes to an aggressive phenotype in a subset of CaP and suggest that ANXA2 has markedly different functions depending on its cellular context. Finally, this is the first description of a role for ANXA2 in IL-6 expression, and ANXA2 represents a new therapeutic target for reducing IL-6 in high-grade prostate cancer.

Annexin A2 Is a Molecular Target for TM601, a Peptide with Tumor-targeting and Anti-angiogenic Effects

“…A knockdown approach using siRNA demonstrated that annexin A2 is required for surface binding of TM601 to Panc-1 cells. Identification of annexin A2 as a specific target for TM601 is consistent with the tumortargeting effects of TM601 and the corresponding overexpression of annexin A2 in multiple human cancers including high grade glioma (17)(18)(19)(20), colorectal cancer (21), pancreatic cancer (22), hepatocellular carcinoma (23,24), renal cell carcinoma (25), squamous cell carcinoma (26), prostate cancer (27), and lung cancer (28). Annexin A2 overexpression has been correlated with poor prognosis in colorectal cancer (21) and recurrence after surgery in pancreatic cancer patients (29).…”

The Role of Annexin A2 in Tumorigenesis and Cancer Progression

“…The increased expression of annexin A2 has been reported in cancers of the breast, liver, prostate and pancreas [6][7][8][9]. Additionally, annexin A2 has also been demonstrated to play a role in cancer cell migration, invasion [7,10] and adhesion [11,12], processes which are essential for cancer metastasis.…”

Annexin A1, A2, A4 and A5 play important roles in breast cancer, pancreatic cancer and laryngeal carcinoma, alone and/or synergistically

“…Attention has now been drawn to whether they also play important roles in other types of cancer. According to previous studies, annexin A2 was also related to prostate cancer, invasive cervical carcinoma and lung cancer (15)(16)(17)18); annexin A4 was involved in gastric cancer and colorectal cancer (2,19); annexin A5 was associated with nasopharyngeal carcinoma and colorectal adenocarcinomas. The results indicated that other proteins, apart from the three annexins, may synergistically affect the progress of the three types of cancer cells.…”