Development of cell internalizing antibody as a safe and nontoxic imaging tool

• Project/Area Number: 23300195
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical systems
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: KAUL Sunil 独立行政法人産業技術総合研究所, バイオメディカル研究部門, 上級主任研究員 (10356751)
• Co-Investigator(Kenkyū-buntansha): WADHWA Renu 独立行政法人産業技術総合研究所, バイオメディカル研究部門, 研究グループ長 (30371090)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: 検査・診断システム / バイオイメージング / 抗モータリン抗体

Research Abstract

In order to develop application of anti-mortalin antibody for diagnostics and delivery, we generated new antibodies and performed a characterization. We found that the cell internalizing and non-internalizing antibodies possess distinctly different epitopes. Mechanism of internalization was determined by adopting multiple inhibitor approach. We found that the antibody internalization was inhibited most strongly by Nystatin, implying that it involves lipid raft mediated endocytosis. We next used specific inhibitors of three raft pathways. The internalization was strongly inhibited by dynamin inhibitor. On the other hand, caveolin-1 inhibitor and CDC42 inhibitor showed weak effect. It was concluded that the internalization of new internalizing anti-mortalin antibodies is mostly mediated by Dynamin and Caveolin dependent endocytosis.

Research Products

• [Journal Article] Targeting of DNA damage signaling pathway induced senescence and reduced migration of cancer cells (2014)
  • Author(s): Gao, R., Singh, R., Kaul, Z., Kaul, S. C., and Wadhwa, R
  • Journal Title: J. Gerontol. A Biol. Sci. Med. Sci Volume: (in press) Issue: 6 Pages: 701-713
  • DOI: 10.1093/gerona/glu019
  • Peer Reviewed
• [Journal Article] Targeting of DNA damage signaling pathway induced senescence and reduced migration of cancer cells. (2014)
  • Author(s): Gao, R., Singh, R., Kaul, Z., Kaul, S. C., and Wadhwa, R.
  • Journal Title: J. Gerontol. A Biol. Sci. Med. Sci. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Mortalin antibody-conjugated quantum dot transfer from human mesenchymal stromal cells to breast cancer cells requires cell-cell interaction (2013)
  • Author(s): Pietilä, M., Lehenkari, P., Kuvaja, P., M., Kaul, S. C., Wadhwa, R., and Uemura T
  • Journal Title: Exp. Cell Res Volume: 319 Issue: 18 Pages: 2770-2780
  • DOI: 10.1016/j.yexcr.2013.07.023
  • Peer Reviewed
• [Journal Article] Molecular interactions of Bcl-2 and Bcl-xL with mortalin : Identification and functional characterization (2013)
  • Author(s): Saxena, N., Katiyar, SP., Liu, Y., Grover, A., Sundar, D., Kaul, S. C., and Wadhwa, R
  • Journal Title: Biosci. Rep Volume: 33 Issue: 5 Pages: 797-806
  • DOI: 10.1042/bsr20130034
  • Peer Reviewed
• [Journal Article] Exercise training upregulates nitric oxide synthases in the kidney of rats with chronic heart failure (2013)
  • Author(s): Ito D, Ito O, Mori N, Suda C, Hao K, Cao P, Muroya Y, Takashima K, Shimokawa H, Kohzuki M
  • Journal Title: Clin Exp Pharma Physiol Volume: 40 Pages: 617-625
  • Peer Reviewed
• [Journal Article] Effects of exercise training on nitric oxide synthase in the kidney of spontaneously hypertensive rats (2013)
  • Author(s): Ito D, Ito O, Cao P, Mori N, Suda T, Muroya Y, Takashima K, Ito S, Kohzuki M
  • Journal Title: Clin Exp Pharma Physiol Volume: 40 Pages: 74-82
  • Peer Reviewed
• [Journal Article] Withanone binds to mortalin and abrogates mortalin-p53 complex : Computational and experimental evidence (2012)
  • Author(s): Grover, A., Priyandoko, D., Gao, R., Shandilya, A., Widodo, N., Bisaria, V. S., Kaul, S. C., Wadhwa, R, and Sundar, D
  • Journal Title: Int. J. Biochem. Cell Biol Volume: 44 Issue: 3 Pages: 496-504
  • DOI: 10.1016/j.biocel.2011.11.021
  • Peer Reviewed
• [Journal Article] Druggability of mortalin for cancer and neuro-degenerative disorders (2012)
  • Author(s): Deocaris, C. C., Lu, W. J., Kaul, S. C., and Wadhwa, R
  • Journal Title: Curr. Pharm. Des Volume: 19 Issue: 3 Pages: 418-429
  • DOI: 10.2174/1381612811306030418
  • Peer Reviewed
• [Journal Article] Withanone binds to mortalin and abrogates mortalin-p53 complex: Computational and experimental evidence (2012)
  • Author(s): Grover, A., Priyandoko, D., Gao, R., Shandilya, A., Widodo, N., Bisaria, V. S., Kaul, S. C., Wadhwa, R, and Sundar, D.
  • Journal Title: Int. J. Biochem. Cell Biol. Volume: 44 Pages: 496-504
• [Journal Article] Druggable mortalin (2012)
  • Author(s): Deocaris, C.C., Lu, W.J., Kaul, S.C., Wadhwa, R.
  • Journal Title: Curr.Pharm.Des. Volume: (掲載確定)(印刷中)
  • Peer Reviewed
• [Presentation] Cell internalizing anti-mortalin antibodies for in vitro and in vivo imaging applications : mechanism (2014)
  • Author(s): Wadhwa, R., Kaul, Z., Na, Y., Ryu, J., Yun, C-O., and Kaul, S
  • Organizer: 日本組織培養学会第87回大会
  • Place of Presentation: 星陵会館(東京都)
  • Year and Date: 2014-05-29
• [Presentation] Mortalin - an hsp70 stress chaperone in human carcinogenesis (2014)
  • Author(s): Wadhwa, R
  • Organizer: Workshop on "Frontiers in Science & Technology"
  • Place of Presentation: シッキム(インド)
• [Presentation] Mortalin - an hsp70 stress chaperone in human carcinogenesis (2014)
  • Author(s): Wadhwa, R.
  • Organizer: Workshop on “Frontiers in Science & Technology”
  • Place of Presentation: シッキム（インド）
  • Invited
• [Presentation] Cell-internalizing anti-mortalin antibodies as imaging tools (2013)
  • Author(s): Kaul, S.C., Na, Y., Ryu, J., Yaguchi, T. and Wadhwa, R
  • Organizer: 日本組織培養学会第86回大会
  • Place of Presentation: 産業技術総合研究所(茨城県)
  • Year and Date: 2013-05-30
• [Presentation] Fate of bone marrow mesenchymal stem cells following the autologous transplantation into a rabbit osteonecrosis model (2013)
  • Author(s): Sugaya, H., Mishima, H., Li, M., Aoto, K., Yoshioka, T., Ogawa, T., Yaguchi, T., Gao, R., Kaul, S., and Wadhwa, R
  • Organizer: 日本組織培養学会第86回大会
  • Place of Presentation: 産業技術総合研究所(茨城県)
  • Year and Date: 2013-05-30
• [Presentation] Cell internalizing anti-mortalin antibodies as imaging tools (2013)
  • Author(s): Ryu, J., Na, Y., Yaguchi, T., Wadhwa, R., and Kaul S
  • Organizer: 日本組織培養学会第86回大会
  • Place of Presentation: 産業技術総合研究所(茨城県)
  • Year and Date: 2013-05-30
• [Presentation] Long term labeling of mesenchymal stem cells by internalizing quantum dots conjugated with anti-mortalin antibody : application to cartilage regeneration and study of cancer cells/stem cells interaction (2013)
  • Author(s): Uemura, T., Yoshioka, T., Pietilae, M., Mishima, H., Long, X., Matsumoto, R., Kaul, S., and Wadhwa, R
  • Organizer: 日本組織培養学会第86回大会
  • Place of Presentation: 産業技術総合研究所(茨城県)
  • Year and Date: 2013-05-30
• [Presentation] Functional characterization of Bcl-2/BclxL-mortalin complexes in human cancer cells (2013)
  • Author(s): Liu, Y., Saxena, N., Sundar, D., Wadhwa, R. and Kaul, S.C
  • Organizer: 日本組織培養学会第86回大会
  • Place of Presentation: 産業技術総合研究所(茨城県)
  • Year and Date: 2013-05-30
• [Presentation] Non-mitochondrial mortalin promotes human tumorigenesis through activation of telomerase and hnRNP-K (2013)
  • Author(s): Ryu, J., Yaguchi, T., Na, Y., Yun, Ch., Kaul, S.C. and Wadhwa, R
  • Organizer: 日本組織培養学会第86回大会
  • Place of Presentation: 産業技術総合研究所(茨城県)
  • Year and Date: 2013-05-30
• [Presentation] Molecular link between cellular aging and carcinogenesis (2013)
  • Author(s): Wadhwa, R
  • Organizer: 10th International Conference on Geriatric Care
  • Place of Presentation: ニューデリー(インド)
• [Presentation] Mortalin-based imaging reagents and technologies (2013)
  • Author(s): Kaul S. C
  • Organizer: BPPT-AIST Joint Symposium on Life Science and Technology Innovation
  • Place of Presentation: ノボテルボゴール(インドネシア)
• [Presentation] Mortalin in health and disease : Insights from cancer and brain derived cells (2013)
  • Author(s): Wadhwa R
  • Organizer: International Symposium on Neuroscience and XXXI Annual Conference of Indian Academy of Neurosciences, The National Academy of Sciences
  • Place of Presentation: アラハバッド(インド)
• [Presentation] In vitro and in vivo approaches to investigate the role of mortalin in human carcinogenesis and neuronal differentiation (2013)
  • Author(s): Wadhwa, R
  • Organizer: IBRO-APRC Associate School of Neuroscience
  • Place of Presentation: バナラスヒンドゥー大学(インド)
• [Presentation] Basic studies on how a stress protein 'mortalin' regulates old age cancers and brain disorders (2013)
  • Author(s): Wadhwa, R and KAUL, S.C
  • Organizer: International Conference on Geriatric Care 2012
  • Place of Presentation: ベルガム(インド)
• [Presentation] Molecular link between cellular aging and carcinogenesis (2013)
  • Author(s): Wadhwa, R
  • Organizer: 10th International Conference on Geriatric Care
  • Place of Presentation: ニューデリー（インド）
  • Invited
• [Presentation] Mortalin-based imaging reagents and technologies (2013)
  • Author(s): Kaul S. C.
  • Organizer: BPPT-AIST Joint Symposium on Life Science and Technology Innovation
  • Place of Presentation: ノボテルボゴール（インドネシア）
• [Presentation] Mortalin in health and disease: Insights from cancer and brain derived cells (2013)
  • Author(s): Wadhwa R.
  • Organizer: International Symposium on Neuroscience and XXXI Annual Conference of Indian Academy of Neurosciences
  • Place of Presentation: アラハバッド（インド）
  • Invited
• [Presentation] In vitro and in vivo approaches to investigate the role of mortalin in human carcinogenesis and neuronal differentiation (2013)
  • Author(s): Wadhwa R.
  • Organizer: IBRO-APRC Associate School of Neuroscience
  • Place of Presentation: バナラスヒンドゥー大学（インド）
  • Invited
• [Presentation] New cell internalizing anti-mortalin antibodies for bio-imaging (2012)
  • Author(s): Yaguchi, T., Ryu, J., Wadhwa, R. and Kaul, S. C
  • Organizer: 第6回ナノ・バイオメディカル学会大会
  • Place of Presentation: 産業技術総合研究所(茨城県)
• [Presentation] Stress chaperone mortalin in mitochondrial functions and age-related neurodegeneration (2012)
  • Author(s): Wadhwa, R. and KAUL, S.C
  • Organizer: 1st World Congress on Healthy Ageing 2012
  • Place of Presentation: クアラルンプール(マレーシア)
• [Presentation] Basic studies on how a stress protein ‘mortalin’ regulates old age cancers and brain disorders. (2012)
  • Author(s): Wadhwa, R
  • Organizer: International Conference on Geriatric Care 2012.
  • Place of Presentation: Belgaum, India
• [Presentation] Functional significance of mortalin in human cancers and neural differentiation (2012)
  • Author(s): Kaul, S.C.
  • Organizer: XXX Annual meeting of Indian Academy of Neurosciences.
  • Place of Presentation: Amritsar, India
• [Presentation] An internalizing antibody conjugated with quantum dot for in vitro and in vivo imaging (2011)
  • Author(s): Kaul, S. C
  • Organizer: Invited Lecture in the Life Sciences Center
  • Place of Presentation: マニパル(インド)
  • Year and Date: 2011-09-25
• [Presentation] An internalizing antibody conjugated with quantum dot for in vitro and in vivo imaging (2011)
  • Author(s): Kaul S.C.
  • Organizer: Invited Lecture in the Life Sciences Center
  • Place of Presentation: Manipal University, Manipal (India)(招待講演)
  • Year and Date: 2011-09-25
• [Presentation] An internalizing antibody based generation of illuminating cells and their real time imaging in vitro and in vivo (2011)
  • Author(s): Kaul, S. C
  • Organizer: 6th Biyani's International Conference 2011 (BIOCON-11) on Innovations In the Latest Healthcare Issues
  • Place of Presentation: ジャイプール(インド)
  • Year and Date: 2011-09-20
• [Presentation] An internalizing antibody based generation of illuminating cells and their real time imaging in vitro and in vivo (2011)
  • Author(s): Kaul S.C.
  • Organizer: 6th Biyani's International Conference 2011 on Innovations In the Latest Healthcare Issues
  • Place of Presentation: Biyani Girls College, Jaipur (India)(招待講演)
  • Year and Date: 2011-09-20
• [Presentation] Cell internalizing anti-mortalin antibodies for in vitro and in vivo imaging applications: mechanism．
  • Author(s): Wadhwa, R., Kaul, Z., Na, Y., Ryu, J., Yun, C-O., and Kaul, S.
  • Organizer: 日本組織培養学会第87回大会
  • Place of Presentation: 星陵会館（東京）
• [Presentation] Long term labeling of mesenchymal stem cells by internalizing quantum dots conjugated with anti-mortalin antibody: application to cartilage regeneration and study of cancer cells/stem cells interaction.
  • Author(s): Uemura, T., Yoshioka, T., Pietilae, M., Mishima, H., Long, X., Matsumoto, R., Kaul, S., and Wadhwa, R.
  • Organizer: 日本組織培養学会第８６回大会
  • Place of Presentation: 産業技術総合研究所（茨城県）
• [Presentation] Cell internalizing anti-mortalin antibodies as imaging tools.
  • Author(s): Kaul, S.C., Na, Y., Ryu, J., Yaguchi, T. and Wadhwa, R.
  • Organizer: 日本組織培養学会第８６回大会
  • Place of Presentation: 産業技術総合研究所（茨城県）
  • Invited
• [Presentation] Fate of bone marrow mesenchymal stem cells following the autologous transplantation into a rabbit osteonecrosis model
  • Author(s): Sugaya, H., Mishima, H., Li, M., Aoto, K., Yoshioka, T., Ogawa, T., Yaguchi, T., Gao, R., Kaul, S., and Wadhwa, R.
  • Organizer: 日本組織培養学会第８６回大会
  • Place of Presentation: 産業技術総合研究所（茨城県）
• [Presentation] Non-mitochondrial mortalin promotes human tumorigenesis through activation of telomerase and hnRNP-K
  • Author(s): Ryu, J., Yaguchi, T., Na, Y., Yun, Ch., Kaul, S.C. and Wadhwa, R.
  • Organizer: 日本組織培養学会第８６回大会
  • Place of Presentation: 産業技術総合研究所（茨城県）
• [Presentation] Functional characterization of Bcl-2/BclxL-mortalin complexes in human cancer cells
  • Author(s): Liu, Y., Saxena, N., Sundar, D., Wadhwa, R. and Kaul, S.C.
  • Organizer: 日本組織培養学会第８６回大会
  • Place of Presentation: 産業技術総合研究所（茨城県）
• [Book] Mortalin Biology: Life, Stress and Death (2012)
  • Author(s): Sunil C Kaul & Renu Wadhwa
  • Publisher: Springer
• [Book] Mortalin Biology : Life, Stress and Death (2012)
  • Author(s): Wadhwa, R., Kaul, S.C.
  • Total Pages: 19
  • Publisher: Springer
• [Book] Mortalin Biology : Life, Stress and Death (2012)
  • Author(s): Deocaris, C.C., Kaul, S.C., Wadhwa R.
  • Total Pages: 11
  • Publisher: Springer
• [Book] Mortalin Biology : Life, Stress and Death (2012)
  • Author(s): Uemura, T., Nishi, M., Kaul, S.C., Wadhwa, R.
  • Total Pages: 12
  • Publisher: Springer
• [Book] Mortalin Biology : Life, Stress and Death (2012)
  • Author(s): Gao, R., Kaul, Z., Yaguchi, T., Wadhwa, R.
  • Total Pages: 17
  • Publisher: Springer
• [Book] Mortalin Biology : Life, Stress and Death (2012)
  • Author(s): Kaul, Z., Wadhwa, R., Kaul, S.C.
  • Total Pages: 15
  • Publisher: Springer