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World J Gastroenterol. Oct 28, 2014; 20(40): 14747-14759
Published online Oct 28, 2014. doi: 10.3748/wjg.v20.i40.14747
SIBLINGs and SPARC families: Their emerging roles in pancreatic cancer
Ferda Kaleağasıoğlu, Martin R Berger
Ferda Kaleağasıoğlu, Visiting Scientist at Toxicology and Chemotherapy Unit, German Cancer Research Center, D-69120 Heidelberg, Germany
Ferda Kaleağasıoğlu, Department of Pharmacology, Faculty of Medicine, University of Yeditepe, 34755 Ataşehir/İstanbul, Turkey
Martin R Berger, Toxicology and Chemotherapy Unit, German Cancer Research Center, D-69120 Heidelberg, Germany
Author contributions: Kaleağasıoğlu F and Berger MR contributed equally to this work and wrote the review.
Correspondence to: Martin R Berger, Professor, Toxicology and Chemotherapy Unit, German Cancer Research Center, Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany. m.berger@dkfz-heidelberg.de
Telephone: +49-6221-423310 Fax: +49-6221-423313
Received: October 23, 2013
Revised: April 19, 2014
Accepted: May 23, 2014
Published online: October 28, 2014
Abstract

Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized by its dense stroma, which is involved in the critical interplay with the tumor cells throughout tumor progression and furthermore, creates a barrier restricting efficient penetration of therapeutics. Alterations in a large number of genes are reflected by a limited number of signaling pathways, which are potential targets. Understanding more about the molecular basis of this devastating cancer type regarding tumor microenvironment, distinct subpopulations of cells, epithelial-to-mesenchymal transition and inflammation will lead to the development of various targeted therapies for controlling tumor growth and metastasis. In this complex scenario of pancreatic cancer, especially members of the “small integrin binding ligand N-linked glycoproteins” (SIBLINGs) and “secreted protein acidic and rich in cysteine” (SPARC) families have emerged due to their prominent roles in properties including proliferation, differentiation, apoptosis, adhesion, migration, angiogenesis, wound repair and regulation of extracellular matrix remodeling. SIBLINGs consist of five members, which include osteopontin (OPN), bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. The SPARC family of modular extracellular proteins is comprised of SPARC/osteonectin (ON) and SPARC-like 1 (hevin); secreted modular calcium binding proteins; testicans and follistatin-like protein. In this review, we especially focus on OPN and ON, elaborating on their special and growing importance in pancreatic cancer diagnosis and prognosis.

Keywords: Pancreatic cancer, Microenvironment, Signaling pathways, Osteopontin, Osteonectin, Hevin, Biomarker, Therapeutic targeting

Core tip: In this article we review the evidence that the protein families “small integrin binding ligand N-linked glycoproteins” (SIBLINGs) and “secreted protein acidic and rich in cysteine” (SPARC) modulate functions like proliferation, differentiation, apoptosis, adhesion, migration, angiogenesis, wound repair, and regulation of extracellular matrix remodeling. Moreover they play significant roles throughout each stage of pancreatic cancer formation and progression. We discuss, with special reference to osteopontin and osteonectin, how SIBLING and SPARC proteins have attracted growing importance as diagnostic and prognostic tools and discuss their fascinating potential as therapeutic targets.