Anti-Syndecan-1 Antibody Development

Equipped with state-of-the-art research and manufacturing facilities, Creative Biolabs is dedicated to helping our clients design and prepare antibodies with high affinity and good specificity to promote the development of your projects. With more than 10 years of experience in monoclonal antibodies (mAbs) preparation and modification, experts at Creative Biolabs can provide customers with comprehensive antibody development services against syndecan-1.

Syndecan-1

Syndecans are a small family of type 1 transmembrane heparan sulfate (HS) proteoglycans and composed of 4 mammalian members, syndecan-1 to syndecan-4. All of them comprise an ectodomain, a single transmembrane domain, and a short cytoplasmic domain. Syndecan-1 (CD138) is expressed by numerous cell types with roles in tumor proliferation, differentiation, adhesion, and migration through their ability to interact with a range of growth factor receptors and integrins.

Fig.1 The syndecan family. (Szatmári, 2013)

Ectodomain Shedding

Syndecan-1 shedding from the cell surface is associated with the invasive phenotype in lung and breast cancers. Shedding is mediated by matrix metalloproteases (MMPs), mainly MMP-7 and 9, generating the biologically active soluble ectodomains and membrane stub. By enhancing growth factor signaling within host cells, shed syndecan-1 wields its powerful effect on tumor behavior primarily through conditioning the tumor microenvironment by binding to extracellular matrix molecules such as collagen and fibronectin. Chemotherapy-induced shedding of syndecan-1 might lead to the establishment of a tumor microenvironment that supports tumor survival and relapse. Additionally, the cells that survive chemotherapy and continue to grow exhibit elevated levels of shedding. This enhanced shedding likely contributes to the rapid disease progression seen following the reemergence of a tumor after chemotherapy.

Fig.2 Localization of cleavage sites on the syndecan ectodomains. (Manon-Jensen, 2013)

Antibody Strategies Against Syndecan-1

Although blocking the activity of different MMPs during chemotherapy diminishes the generation of shed syndecan-1, it is not reliable to specifically block syndecan-1 shedding in vivo with sheddase inhibitors because different proteases with broad substrate specificities contribute to this process causing side effects and lack of efficacy. Except for being a promising candidate marker for cytopathological diagnosis and prognostication, shed syndecan-1 could be regarded as a target to develop antibodies to neutralize its functions. Besides, now that some cleavage sites on the syndecan-1 ectodomains are already known, antibodies could be developed against these sites to make syndecan keep away from shedding, followed by conjugated with drugs to make antibody-drug conjugate (ADC) or combined with existing chemotherapy. These approaches will both significantly dampen tumor relapse and prevent aggressive progression of cancer.

Creative Biolabs provides customized antibody development services against tumor surface protein shedding from cells by advanced technology platform to help your projects. With novel technology platform and professional experiment services, Creative Biolabs gets ready to provide you with the best antibody services. Please feel free to contact us for more details.

References

1. Szatmári, T.; Dobra, K. The role of syndecan-1 in cellular signaling and its effects on heparan sulfate biosynthesis in mesenchymal tumors. Frontiers in oncology. 2013, 3, 310.
2. Manon-Jensen, T.; et al. Mapping of matrix metalloproteinase cleavage sites on syndecan-1 and syndecan-4 ectodomains. The FEBS journal. 2013, 280(10), 2320-2331.

For Research Use Only. NOT FOR CLINICAL USE.