S100A4 antibodies are critical for:
Biomarker Detection: Immunohistochemistry (IHC) reveals S100A4 overexpression in aggressive cancers (e.g., lung, prostate) and correlates with poor prognosis .
Functional Studies:
Mechanistic Insights: Antibodies disrupt S100A4 interactions with receptors like RAGE and TLR4, which drive pro-inflammatory and metastatic pathways .
Metastasis Suppression: Anti-S100A4 monoclonal antibodies (e.g., mAb6B12) reduce lung metastasis in xenograft models by inhibiting stromal cell recruitment and cytokine production (e.g., IL-6, RANTES) .
Immunomodulation: In prostate cancer models, antibody therapy shifts Th1/Th2 balance, enhancing anti-tumor immunity .
Prognostic Value: High S100A4 levels in serum or biopsies predict poor response to androgen deprivation therapy (ADT) and increased mortality in prostate cancer .
Targeted Therapy: Phase I trials suggest antibodies are well-tolerated, with ongoing studies exploring combinatorial regimens .
Specificity Concerns: Off-target binding to other S100 proteins necessitates rigorous validation using knockout controls .
Dual Roles of S100A4: While promoting metastasis, S100A4 also has physiological roles in neurogenesis and wound healing, complicating therapeutic targeting .
S100 Calcium Binding Protein A4 (S100A4), also known as metastasin, is a member of the S100 family of proteins. These proteins are characterized by their ability to bind calcium ions through EF-hand motifs, which are helix-loop-helix structural domains . S100A4 is encoded by the S100A4 gene located on chromosome 1q21 in humans .
S100A4 contains two EF-hand calcium-binding domains and is primarily localized in the cytoplasm and/or nucleus of cells . The protein is expressed in a variety of tissues, including the synovial joint, monocytes, granulocytes, and the palpebral conjunctiva . In mice, S100A4 is expressed in tissues such as the lip, lens, ovary, esophagus, urinary bladder, spleen, and white adipose tissue .
S100A4 plays a crucial role in several cellular processes:
S100A4 is notably implicated in cancer progression and metastasis. It supports tumorigenesis by stimulating angiogenesis and enhancing the invasive capabilities of cancer cells . Research has shown that S100A4 synergizes with vascular endothelial growth factor (VEGF) to promote endothelial cell migration and increase matrix metalloproteinase-9 (MMP-9) activity .