Page 27 - D. Cancer biology
P. 27

Replenishing SOCS3 Suppresses
                                  Pancreatic Cancer Progression

         Sukyeong Jeong, Shinyoung Park, Jaehyeon Kim, Chohyun Kim, Mikyung Kim, Youngsil Choi, and Daewoong Jo
                    SOCS3 Team,  Cellivery R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, Korea

                   BACKGROUND                                                   AIM
    Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator
    of Janus kinase/signal transducers and activators of transcription  The aim of this study is to evaluate a recombinant SOCS3 protein
    (JAK/STAT) signaling, through which it plays pivotal roles in cancer  engineered to improve cell- and tissue-permeability, iCP-SOCS3,
    progression. It suggests therapeutic potential of intracellularly  functions as a tumor suppressor in progression of pancreatic
    delivery SOCS3 recombinant protein to target tumors that depends  cancer.
    on JAK/STAT signaling for growth or survival.
                                                 METHODS

   A recombinant cell-permeable SOCS3 protein with an advanced macromolecule transduction domain (aMTD) and a solubilization domain,
   namely improved cell-permeable (iCP)-SOCS3, was purified and investigated that whether it has increased yield, solubility, cell permeability and
   biological activities to inhibit pancreatic cancer growth and tumor cell invasive behaviors.

                                                 RESULTS

           Figure 1. iCP-SOCS3 Shows High Solubility/Yield      Figure 4. iCP-SOCS3 Suppresses Tumor Growth in
                   & High Cell-Permeability                  Subcutaneous Tumor Xenografts of Pancreatic Cancer Cells
                          B            C               A
      A                                                                         D
                                               421 fold




                           E
                                                       B              C
     D                                                                           E





           Figure 2. iCP-SOCS3 Suppresses Proliferation &
               Apoptosis of Pancreatic Cancer Cells
                                                             Figure 5. iCP-SOCS3 Suppresses Tumor Growth By inhibiting
   A                                                         Phosphorylation of STATs in Orthotopic Xenograft Models
                                                         A                      B



   B                         C



                                                                     Figure 6. iCP-SOCS3 Is Accumulated
                                                             In Target Tissue (Pancreatic Tumor) of Tumor-Bearing Mice


            Figure 3. iCP-SOCS3 Suppresses Migration &   A                     B
                Invasion of Pancreatic Cancer Cells
   A                      B                                                                           2.27








            CONCLUSION                           REFERENCES                      Contact information
   These results provide further evidence that  Chung et al. (2020) Science Advances, 6: eaba 1193  Minyong Jung
   SOCS3 can function as a tumor suppressor  Lim et al. (2013) Clinical Cancer Research, 19: 680-690  New Drug & Business Development
   and establish intracellular SOCS3 delivery as a  Lim et al. (2013) Biomaterials, 34: 6261-6271
   potential protein therapy for pancreatic cancer  Lim et al. (2012) Molecular Therapy, 20: 1540-1549  Cellivery Therapeutics, Inc.
   by negatively regulating JAK/STAT signaling.
                                        Jo et al (2005) Nature Medicine, 11: 892-898  jungmy@cellivery.com
                                        Jo et al (2001) Nature Biotechnology, 19: 929-933  +82-2-3151-8900
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