An important cancer marker CD340

CD340, also known as ErbB2, HER2 or Neu, is a 185 kDa type I transmembrane glycoprotein with tyrosine kinase activity.  Unlike three other members of epidermal growth factor receptor family (HER1/EGFR, HER3, and HER4) it has no known activating ligand and its extracellular domain is in permanently activated form. Upon ligand-mediated activation of EGFR, HER3 or HER4, this tyrosine kinase easily heterodimerizes with them, which results in potent stimulation of cellular responses that vary depending on the ligand and the cell type, and are essential for cell growth and differentiation. This plays important roles in proper development of multiple structures and systems in the organism, including nervous system, skin, and epithelia of the mammary gland, gastrointestinal, respiratory, reproductive and urinary tracts. On the other hand, CD340 overexpression is associated with cancerogenesis in these tissues, as it promotes not only cell proliferation, but also their invasive phenotype. In case of overexpression, CD340 functions mainly in homodimers.  Not only CD340 overexpression is associated with many cancer types, but it is also a marker of poor prognosis. Hence CD340 has become a target for various therapies, and some of them brought significant improvement of the disease outcome.   
 
 

Fig. 1: Whereas EGFR, HER4 (not shown) and HER3 need their ligands to get into active conformation, CD340 is active without any ligand. As a result, when CD340 is overexpressed, it is able to initiate downstream signaling by phosphorylating its own tyrosine-based activation motifs spontaneously in homodimers. Interestingly, although HER3 does not have functional tyrosine kinase (TK) domain, CD340/HER3 heterodimer provides strong mitogenic signal.
 
 
The mouse monoclonal antibody 24D2 recognizes an extracellular epitope of human CD340, and can be used for flow cytometry and immunocytochemistry.  Formats:  Purified (11-832-C100), FITC (1F-832-T100), PE (1P-832-T100), APC (1A-832-T100).
 
 

Fig. 2: Separation of MCF-7 cells stained using anti-human CD340 (24D2) APC antibody (10 μl reagent per million cells in 100 μl of cell suspension, red-filled) from MCF-7 cells stained using mouse IgG1 isotype control (MOPC-21) APC antibody (concentration in sample 3 μg/ml, the same as CD340 APC concentration; black-dashed) in flow cytometry analysis (surface staining) of MCF-7 cell suspension.
 
 
 
Further reading:
 
Hou Y et al.: The assessment of HER2 status and its clinical implication in breast cancer. Diag. Histopathol. 2020, 26(2):61-68.
 
Alrhmoun S and Sennikov S: The role of tumor-associated antigen HER2/neu in tumor development and the different approaches for using it in treatment: Many choices and future directions. Cancers 2022, 14, 6173.
 
Amisha F et al.: A comprehensive review on the role of human epidermal growth factor receptor 2 (HER2) as a biomarker in extra-mammary and extra-gastric cancers. Onco 2023, 3:96-124.
 
Yang Z et al.: Resistance to anti-HER2 therapy associated with the TSC2 nonsynonymous variant c.4349 C > G (p.Pro1450Arg) is reversed by CDK4/6 inhibitor in HER2-positive breast cancer. NPJ Breast Cancer 2023 May 9;9(1):36.
 
 

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