Strategies to overcome 5-FU resistance in cancer

Congratulations to the Selbo laboratory for their recent publication using Anti-CD105-SAP. This targeted toxin was previously part of the BETA program. As first to publish using this product, Selbo’s group receives a $500 product credit and applause for their great work.

5-Fu Resistant Emt-Like Pancreatic Cancer Cells Are Hypersensitive to Photochemical Internalization of the Novel Endoglin-Targeting Immunotoxin CD105-Saporin. Lund K, Olsen CE, Wong JJW, Olsen PA, Solber, NT, Hogset A Krauss S, Selbo PK. (2017). Journal of Experimental & Clinical Cancer Research, 36 (1):187.

CD105 is also known as Endoglin and it modulates cellular response to TGF-β, involved in vascular development and remodeling. It is a type I integral membrane homodimer protein with subunits of 90 kD found on vascular endothelial cells, bone marrow stromal cells, and hematopoietic stem/progenitor cells. CD105 is weakly expressed on stromal fibroblasts. It is also expressed on activated monocytes and tissue macrophages.

Expression of CD105 is increased on activated endothelium in tissues undergoing angiogenesis, such as in tumors, or in cases of wound healing or dermal inflammation. CD105 is a component of the TGF-β receptor system in human umbilical vein endothelial cells and binds TGF-β1 and β3 with high affinity but does not bind to TGF-β2.

Anti-CD105-SAP eliminates cells expressing human CD105 (Endoglin).  All other cells are left untouched.

Anti-CD105-SAP (Cat. #IT-80)

Dose:  Cells were seeded (3000/well) in 96-well plates and allowed to attach overnight. The cells were incubated with the Anti-CD105-saporin (2.4 nM) or Saporin as a control (6.48 nM; Saporin was added in a molecular ratio of 2.7:1 to the immunotoxin) giving an equal ratio of Saporin to immunotoxin), with or without the photosensitizer TPCS2a (0.35 μg/ml) for 18 h.

Objective: Investigate resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma.

Summary:   Expression of CD105 was investigated using RT-qPCR, western blotting, flow cytometry, and fluorescence microscopy, and co-localization of TPCS2a and Anti-CD105-SAP was assessed using microscopy. MTS assay was used to investigate cytotoxic effects of photochemical internalization of Anti-CD105-SAP. For the first time, we demonstrate the promise of PCI-based targeting of CD105 in site-specific elimination of 5-FU resistant pancreatic cancer cells using Anti-CD105-SAP in vitro. PCI-based targeting of CD105 may represent a potent anti-cancer strategy and should be further evaluated in preclinical models.

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