Inhibition of growth, invasion, and metastasis of human pancreatic carcinoma cells by NK4 in an orthotopic mouse model

Daisaku Tomioka, Naoki Maehara, Keiji Kuba, Kazuhiro Mizumoto, Masao Tanaka, Kunio Matsumoto, Toshikazu Nakamura

研究成果: ジャーナルへの寄稿記事

139 引用 (Scopus)

抄録

Hepatocyte growth factor (HGF) is involved in malignant behavior of cancers as a mediator in tumor-stromal interactions through enhancing tumor invasion and metastasis. We found recently that NK4, a four-kringle fragment of HGF, functions as both an HGF-antagonist and an angiogenesis inhibitor. We have now determined whether blockade of the HGF-c-Met/HGF receptor pathway and tumor angiogenesis by administration of recombinant NK4 would inhibit growth, invasion, and metastasis of human pancreatic carcinoma implanted into the pancreas of nude mice. When treatment with NK4 or anti-HGF neutralizing antibody was initiated from the third day after orthotopic injection of SUIT-2 human pancreatic cancer cells, both NK4 and anti-HGF antibody suppressed the conversion of orthotopic pancreatic tumors from carcinoma in situ to aberrantly invading cancers during days 3-14. On the other hand, when the treatment was begun on day 10, a time when cancer cells were already invading surrounding tissues, NK4 but not anti-HGF antibody inhibited tumor growth, peritoneal dissemination, and ascites accumulation at 4 weeks after the inoculation. Antitumor effects of NK4 correlated with decreased microvessel density in pancreatic tumors thereby indicating that the antlangiogenic activity of NK4 may have mainly contributed to its antitumor effects. Moreover, although NK4-treatment was initiated from the end stage (day 24 after tumor inoculation), NK4 prolonged survival time of mice, and the suppression of peritoneal dissemination, ascites accumulation, and invasion of metastasized cancer cells into the peritoneal wall were remarkable. We propose that simultaneous targeting of both tumor angiogenesis and the HGF-mediated invasion-metastasis may prove to be a new approach to treating patients with pancreatic cancer.

元の言語英語
ページ(範囲)7518-7524
ページ数7
ジャーナルCancer Research
61
発行部数20
出版物ステータス出版済み - 10 15 2001

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Hepatocyte Growth Factor
Neoplasm Metastasis
Growth
Neoplasms
Pancreatic Neoplasms
Ascites
Pancreatic Carcinoma
Inhibition (Psychology)
Kringles
Proto-Oncogene Proteins c-met
Neoplasm Antibodies
Angiogenesis Inhibitors
Carcinoma in Situ
Microvessels
Neutralizing Antibodies
Nude Mice
Pancreas
Therapeutics
Injections
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Tomioka, D., Maehara, N., Kuba, K., Mizumoto, K., Tanaka, M., Matsumoto, K., & Nakamura, T. (2001). Inhibition of growth, invasion, and metastasis of human pancreatic carcinoma cells by NK4 in an orthotopic mouse model. Cancer Research, 61(20), 7518-7524.

Inhibition of growth, invasion, and metastasis of human pancreatic carcinoma cells by NK4 in an orthotopic mouse model. / Tomioka, Daisaku; Maehara, Naoki; Kuba, Keiji; Mizumoto, Kazuhiro; Tanaka, Masao; Matsumoto, Kunio; Nakamura, Toshikazu.

:: Cancer Research, 巻 61, 番号 20, 15.10.2001, p. 7518-7524.

研究成果: ジャーナルへの寄稿記事

Tomioka, D, Maehara, N, Kuba, K, Mizumoto, K, Tanaka, M, Matsumoto, K & Nakamura, T 2001, 'Inhibition of growth, invasion, and metastasis of human pancreatic carcinoma cells by NK4 in an orthotopic mouse model', Cancer Research, 巻. 61, 番号 20, pp. 7518-7524.
Tomioka, Daisaku ; Maehara, Naoki ; Kuba, Keiji ; Mizumoto, Kazuhiro ; Tanaka, Masao ; Matsumoto, Kunio ; Nakamura, Toshikazu. / Inhibition of growth, invasion, and metastasis of human pancreatic carcinoma cells by NK4 in an orthotopic mouse model. :: Cancer Research. 2001 ; 巻 61, 番号 20. pp. 7518-7524.
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abstract = "Hepatocyte growth factor (HGF) is involved in malignant behavior of cancers as a mediator in tumor-stromal interactions through enhancing tumor invasion and metastasis. We found recently that NK4, a four-kringle fragment of HGF, functions as both an HGF-antagonist and an angiogenesis inhibitor. We have now determined whether blockade of the HGF-c-Met/HGF receptor pathway and tumor angiogenesis by administration of recombinant NK4 would inhibit growth, invasion, and metastasis of human pancreatic carcinoma implanted into the pancreas of nude mice. When treatment with NK4 or anti-HGF neutralizing antibody was initiated from the third day after orthotopic injection of SUIT-2 human pancreatic cancer cells, both NK4 and anti-HGF antibody suppressed the conversion of orthotopic pancreatic tumors from carcinoma in situ to aberrantly invading cancers during days 3-14. On the other hand, when the treatment was begun on day 10, a time when cancer cells were already invading surrounding tissues, NK4 but not anti-HGF antibody inhibited tumor growth, peritoneal dissemination, and ascites accumulation at 4 weeks after the inoculation. Antitumor effects of NK4 correlated with decreased microvessel density in pancreatic tumors thereby indicating that the antlangiogenic activity of NK4 may have mainly contributed to its antitumor effects. Moreover, although NK4-treatment was initiated from the end stage (day 24 after tumor inoculation), NK4 prolonged survival time of mice, and the suppression of peritoneal dissemination, ascites accumulation, and invasion of metastasized cancer cells into the peritoneal wall were remarkable. We propose that simultaneous targeting of both tumor angiogenesis and the HGF-mediated invasion-metastasis may prove to be a new approach to treating patients with pancreatic cancer.",
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AU - Tanaka, Masao

AU - Matsumoto, Kunio

AU - Nakamura, Toshikazu

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