Role of periostin in cancer progression and metastasis: Inhibition of breast cancer progression and metastasis by anti-periostin antibody in a murine model

Abstract

Abstract. Periostin (PN), a secreted adhesion-related protein expressed in the periosteum and periodontal ligaments, acts as a critical regulator of the formation and maintenance of bone and teeth, and also plays an important role in tumorigenesis. Although PN is highly expressed in various types of human cancers, its function is still unclear. In this study, we focused on the exon 17 region of PN, which is alternatively spliced out. To investigate the function of full-length PN with exon 17, we produced a neutralizing antibody (PN1-Ab) against the peptide encoded by exon 17. In vivo, administration of PN1-Ab significantly inhibited the growth of primary tumors as well as metastatic tumors, associated with prevention of bone destruction, resulting in increased survival of mice. consistent with in vivo data, the present in vitro study demonstrated that addition of full-length PN significantly inhibited cell adhesion and detached adherent cells, while PN1-Ab inhibited the action of PN in a dose-dependent manner. In addition, PN1-Ab significantly inhibited the proliferation, migration and invasion of 4T1 mouse breast cancer cells, which produced PN. Interestingly, PN1-Ab also inhibited the differentiation of osteoclasts. Overall, the present study demonstrated that PN plays a pivotal role in the progression and metastasis of breast cancer. Since administration of PN1-Ab prolonged cell survival through inhibition of the progression and metastasis of 4T1 cells, further development of the PN1-Ab such as generation of a humanized antibody may provide a new therapeutic agent against breast cancer.

Rat Mammary Extracellular Matrix Composition and Response to Ibuprofen Treatment During Postpartum Involution by Differential GeLC–MS/MS Analysis

“…Periostin decreases in abundance with involution and levels remain low in mammary involution ECM following postpartum ibuprofen treatment (Table 3). Potentially due to interactions with integrins that promote cell adhesion and spreading, POSTN has been shown to promote tumor growth and metastasis of breast and ovarian tumor cells in vitro [54]. Roles for POSTN in the normal mammary gland as well as with mammary tumor progression remain largely unknown.…”

The role of periostin in neoplastic processes

“…POSTN has a characteristic structure ( Figure 1) consisting of four main domains, namely an N-terminus (encoded by exon 1) containing a signal peptide (SP), a cysteine-rich EMI domain (exons 2 and 3) made up of approximately 75 amino acids, and a tandem of four homologous FAS1 domains (exons [3][4][5][6][7][8][9][10][11][12][13][14]. The FAS1 domain is a structural homolog of an insect cell adhesion protein fasciclin I and acts as ligand for cell membrane integrins.…”

“…[2] (Figure 1). POSTN isoforms are composed of 751-836 amino acids, and have molecular masses from 83 to 93 kDa [2,11]. The individual isoforms have been identified in various tissues: isoform 1 in human osteosarcomas, isoform 2 in the placenta, isoform 3 in epithelial ovarian carcinoma, and isoforms 2 and 4 in both the normal tissue and cancerous tissue of the urinary bladder [1,2,[12][13][14].…”

Loss of periostin/OSF-2 in ErbB2/Neu-driven tumors results in androgen receptor-positive molecular apocrine-like tumors with reduced Notch1 activity

“…However, previous data have shown that Postn plays a critical role in the establishment of tumor cell niche at secondary sites [22]. Supporting this, administration of Postn neutralizing antibodies in xenograft models of breast and ovarian cancers also suppressed invasion and metastasis [45,46]. …”