CALCB Antibody

Introduction to CALCB Antibody

The CALCB antibody is a specific immunological reagent designed to target the calcitonin-related polypeptide β (CALCB), a neuropeptide primarily expressed in the central nervous system and associated with vasodilation, immune modulation, and tumor progression. CALCB is a CGRP (calcitonin gene-related peptide) variant and interacts with receptor complexes involving RAMP1 (receptor activity-modifying protein 1) to mediate signaling pathways .

Key Properties of CALCB Antibody

**2.1. Immunohistochemistry (IHC) in Autoimmune Pancreatitis (AIP)

CALCB antibodies are utilized to study βCGRP expression in pancreatic tissues. In AIP patients with CALCB splice mutations (e.g., p.Ser30Pro, IR), βCGRP immunoreactivity shifts from neuronal to inflammatory cells surrounding pancreatic nerve fibers and microvasculature . This localization correlates with autoimmune inflammation and ERK1/2 phosphorylation defects .

**2.2. Role in Ewing Sarcoma (EwS)

CALCB is overexpressed in EwS due to transcriptional regulation by the EWSR1-FLI1 fusion protein. CALCB antibodies detect its secretion in EwS cell lines and validate its role in tumor growth via the CGRP/RAMP1 axis .

**2.3. Pancreatic Ductal Adenocarcinoma (PDAC)

Methylation analysis of CALCA and CALCB in PDAC reveals hypermethylation patterns linked to reduced expression. CALCB antibodies aid in assessing these epigenetic changes and their impact on AKT/CREB signaling .

**4.1. Subcellular Localization and Trafficking

Mutations in CALCB splice regions (e.g., p.Ser30Pro) disrupt βCGRP trafficking, reducing ER/Golgi co-localization and secretion. HEK293 studies show mutant βCGRP propeptides exhibit ~50–33% wild-type expression levels in supernatants and lysates .

**4.2. ERK1/2 Phosphorylation and Inflammation

CALCB mutations (p.Ser30Pro, IR) decrease ERK1/2 phosphorylation, impairing anti-inflammatory signaling. This dysregulation promotes leukocyte infiltration and pancreatic damage in AIP .

**4.3. CALCB/RAMP1 Axis in Tumorigenesis

In EwS, CALCB binds to RAMP1-containing CGRP receptors, enhancing cAMP signaling and tumor growth. Knockdown of CALCB or RAMP1 reduces clonogenic growth and tumorigenicity in vitro and in vivo .

**5.1. CGRP Receptor Inhibitors in EwS

Small-molecule inhibitors (e.g., MK-3207, BIBN-4096) targeting the CGRP/RAMP1 axis show efficacy in reducing EwS growth. These agents mimic the effects of CALCB knockdown .

**5.2. Anti-CGRP Monoclonal Antibodies in Migraine

While not directly targeting CALCB, anti-CGRP therapies (e.g., erenumab, fremanezumab) highlight the potential of neuropeptide-targeted therapies. CALCB’s role in neurovascular signaling may expand therapeutic horizons .