Annexin II/Annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer

Abstract

One of the most life-threatening complications of prostate cancer is skeletal metastasis. In order to develop treatment for metastasis, it is important to understand its molecular mechanisms. Our work in this field has drawn parallels between hematopoietic stem cell and prostate cancer homing to the marrow. Our recent work demonstrated that annexin II expressed by osteoblasts and endothelial cells plays a critical role in niche selection. In this study, we demonstrate that annexin II and its receptor play a crucial role in establishing metastasis of prostate cancer. Prostate cancer cell lines migrate toward annexin II and the adhesion of prostate cancer to osteoblasts and endothelial cells was inhibited by annexin II. By blocking annexin II or its receptor in animal models, short-term and long-term localization of prostate cancers are limited. Annexin II may also facilitate the growth of prostate cancer in vitro and in vivo by the MAPK pathway. These data strongly suggest annexin II and its receptor axis plays a central role in prostate cancer metastasis, and that prostate cancer utilize the hematopoietic stem cell homing mechanisms to gain access to the niche.

Mechanisms of multiple myeloma bone disease

“…AXII is a recently identified factor produced by stromal cells and osteoclasts that is important in osteoclast formation, hematopoietic stem cell mobilization and homing of prostate cancer cells to the bone. 75 AXII has been previously found to be upregulated in myeloma, and myeloma-derived AXII increases proliferation of myeloma cell lines, possibly through an autocrine mechanism. 76,77 D ' Souza et al 29 recently reported that AXII secreted by osteoclast and stromal cells enhances the growth of multiple myeloma cells in the bone marrow by binding to the AXII receptor on myeloma cells, primarily through a paracrine mechanism.…”

WOMEN IN CANCER THEMATIC REVIEW: Ovarian cancer–peritoneal cell interactions promote extracellular matrix processing

“…Annexin A2-dependent plasmin generation has been demonstrated to be essential for the invasion and migration of invasive breast cancer cells (Sharma et al 2006). Annexin A2 increases cancer cell proliferation and cell survival via the ERK1/2 and MAPK pathway (Shiozawa et al 2008) and is a substrate for src kinase and regulates tyrosine 23 phosphorylation of annexin A2 to enhance cancer cell invasion (Zheng et al 2011). Annexin A2 also plays a role in actin cytoskeletal rearrangement and regulates cancer cell migration (Zhao et al 2010).…”

Breast Cancer Metastases to Bone: Role of the Microenvironment

“…Blocking annexin II or its receptor limited the localization of prostate cancer cells to osteoblasts and endothelial cells (111). In keeping, the inhibition of the SDF-1/CXCL12 and annexin II signaling was shown to inhibit breast cancer progression (112,113).…”