Stanniocalcin-2 (STC2) is a secreted, disulfide-linked homodimeric glycoprotein hormone that belongs to the stanniocalcin family. This family of proteins was initially discovered in fish, specifically in the corpuscles of Stannius, which are endocrine glands located on the surface of the fish kidney . The primary function of stanniocalcins in fish is to regulate calcium and phosphate homeostasis by reducing calcium influx .
Human STC2 was identified as a paralog of STC1 through the search of the STC1-related Expressed Sequence Tag database . STC2 shares 34% identity with human STC1 and eel STC based on sequencing analysis . Phylogenetically, STC2 is highly conserved in vertebrates, including common animal models such as Danio rerio (zebrafish), Xenopus tropicalis (frog), Mus musculus (mouse), and Rattus norvegicus (rat), indicating its significant role in species preservation during evolution .
STC2 is expressed in a wide variety of tissues, including the kidney, ovary, bone, neurons, and muscle . It plays a crucial role in various biological processes, such as tissue remodeling, cell survival, and stress responses . The expression of STC2 is regulated at both transcriptional and post-transcriptional levels and is significantly stimulated under stress conditions like ER stress, hypoxia, and nutrient deprivation .
STC2 facilitates cells in dealing with stress conditions and prevents apoptosis . It also promotes the development of acquired resistance to chemo- and radio-therapies . Additionally, STC2 overexpression has been reported to promote cell proliferation, migration, and immune response . These properties make STC2 a potential biomarker and therapeutic target in various cancers .
Recombinant human STC2 is typically produced using mouse myeloma cell lines (NS0-derived) and is purified to a high degree of purity (>95%) using SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining . The protein is lyophilized from a 0.2 μm filtered solution in PBS and can be reconstituted at 500 μg/mL in PBS .
STC2 has been implicated in various malignancies, including breast, colorectal, stomach, esophageal, prostate, kidney, liver, bone, ovary, and lung cancers . Its overexpression is positively correlated with tumor growth, invasion, metastasis, and patient prognosis . Therefore, STC2 serves as a universal tumor biomarker and a potential therapeutic target .