Periostin and its emerging role in systemic carcinogenesis

Abstract

Dear Editor, I read with great interest the recent article by Merle et al. [1] periostin may also play a major role in carcinogenesis and tumor progression in a number of systemic malignancies besides its role in bone metabolism. For instance, periostin augments lymph angiogenesis in head and neck malignancies. It mediates this effect directly by enhancing tube formation of lymphatic endothelial cells as well as by upregulating the expression of vascular endothelial growth factor C [2]. Akt is responsible in part for periostininduced lymph angiogenesis in head and neck squamous cell carcinomas. Similarly, increased upregulation of periostin expression is seen in nasopharyngeal carcinomas, and it significantly influences the stage of the tumor. Reduced overall survival is typically seen in nasopharyngeal carcinomas with accentuated periostin expression, and periostin in fact is an independent prognostic indicator [3]. Similarly, accentuated periostin expression is seen in nearly 31 % of breast carcinomas [4]. Patients with increased periostin expression tend to show a poor clinical outcome and poor disease-specific survival. Triple negative breast carcinomas typically tend to show higher periostin levels. In fact, periostin is an independent parameter influencing tumor prognosis in mammary malignancies as it is closely related to tumor stage as well as grade [2]. Interestingly, the risk of tumor metastasis in patients with high periostin expression is augmented by accentuated collagen triple helix repeat containing 1 (CTHRC1) expression [5]. Recently, a periostin neutralizing antibody, PN1-Ab, has been developed, and it attenuates tumor growth of the primary breast carcinoma in animal models [6]. The antibody also increases survival rates by decreasing bone destruction as well as distant metastasis. Similarly, upregulation of periostin is seen in non-small cell lung carcinomas [7]. Typically, higher levels are seen in pulmonary adenocarcinomas in contrast to comparatively lower levels in squamous cell pulmonary carcinomas [3]. Periostin expression correlates closely with tumor differentiation and grade [8]. Larger tumors tend to have higher periostin levels indicating its role in tumor progression and invasiveness. Similarly, accentuated expression of periostin is seen in 34% of prostate malignancies. The periostin expression closely correlates with the tumor stage [9]. Similarly, a close association has been seen between high periostin expression and highGleason scores as well as decreased PSA relapse-free survival times [4, 6]. This makes periostin a possible therapeutic target in the management of prostate carcinomas. Similarly, periostin plays a role in enhancing tumor growth in cholangiocarcinomas. It has modulatory effect on a PI3K/AKT-dependent pathway resulting in the ultimate activation of the integrin ITGα5β1 [10]. Increased expression of intracellular pAKT is seen as a result, which facilitates increased invasiveness of the primary tumor. An increased periostin serum level is one emerging way to distinguish cholangiocarcinomas from liver malignancies [11]. The above examples clearly illustrate the significant role that periostin plays in systemic carcinogenesis and the urgent need to identify treatment modalities to modulate periostin expression.