Top

Published in:

01-03-2013 | Research Paper

Macrophage stimulating protein promotes liver metastases of small cell lung cancer cells by affecting the organ microenvironment

Authors: Seidai Sato, Masaki Hanibuchi, Takuya Kuramoto, Nodoka Yamamori, Hisatsugu Goto, Hirohisa Ogawa, Atsushi Mitsuhashi, Trung The Van, Soji Kakiuchi, Shin-ichi Akiyama, Yasuhiko Nishioka, Saburo Sone

Published in: Clinical & Experimental Metastasis | Issue 3/2013

Abstract

The organ microenvironment significantly affects the processes of cancer metastasis. Elucidating the molecular mechanisms of interaction between tumor cells and the organ microenvironment is crucial for the development of effective therapeutic strategies to eradicate cancer metastases. Macrophage stimulating protein (MSP), an activator of macrophages, regulates a pleiotropic array of effects, including proliferation, cellular motility, invasiveness, angiogenesis, and resistance to anoikis. However, the role of MSP in cancer metastasis is still largely unknown. In this study, the action of MSP on the production of metastases was determined in a multiple-organ metastasis model. The murine MSP gene was transfected into two human SCLC cell lines, SBC-5 and H1048, to establish transfectants secreting biologically active MSP. MSP gene transduction did not affect cell proliferation and motility in vitro. Intravenously inoculated MSP transfectants produced significantly larger numbers of liver metastases than parental cells or vector control clones, while there were no significant differences in bone or lung metastases among them. Immunohistochemical analyses of liver metastases revealed that tumor-associated microvessel density and tumor-infiltrating macrophages were significantly increased in lesions produced by MSP transfectants. MSP could stimulate the migration of murine macrophages and endothelial cells in vitro. Consequently, MSP may be one of the major determinants that affects the properties of tumor stroma and that produces a permissive microenvironment to promote cancer metastasis.

Sone S, Yano S (2007) Molecular pathogenesis and its therapeutic modalities of lung cancer metastasis to bone. Cancer Metastasis Rev 26:685–689PubMedCrossRef

Skeel A, Yoshimura T, Showalter SD, Tanaka S, Appella E, Leonard EJ (1991) Macrophage stimulating protein: purification, partial amino acid sequence, and cellular activity. J Exp Med 173:1227–1234PubMedCrossRef

Bezerra JA, Witte DP, Aronow BJ, Degen SJ (1993) Hepatocyte-specific expression of the mouse hepatocyte growth factor-like protein. Hepatology 18:394–399PubMed

Yoshimura T, Yuhki N, Wang MH, Skeel A, Leonard EJ (1993) Cloning, sequencing, and expression of human macrophage stimulating protein (MSP, MST1) confirms MSP as a member of the family of kringle proteins and locates the MSP gene on chromosome 3. J Biol Chem 268:15461–15468PubMed

Wang MH, Skeel A, Leonard EJ (1996) Proteolytic cleavage and activation of pro-macrophage-stimulating protein by resident peritoneal macrophage membrane proteases. J Clin Invest 97:720–727PubMedCrossRef

Nanney LB, Skeel A, Luan J, Polis S, Richmond A, Wang MH, Leonard EJ (1998) Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury. J Invest Dermatol 111:573–581PubMedCrossRef

Ronsin C, Muscatelli F, Mattei MG, Breathnach R (1993) A novel putative receptor protein tyrosine kinase of the met family. Oncogene 8:1195–1202PubMed

Gaudino G, Follenzi A, Naldini L, Collesi C, Santoro M, Gallo KA, Godowski PJ, Comoglio PM (1994) RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. EMBO J 13:3524–3532PubMed

Iwama A, Yamaguchi N, Suda T (1996) STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among the HGF receptor family. EMBO J 15:5866–5875PubMed

10.

Peace BE, Hughes MJ, Degen SJ, Waltz SE (2001) Point mutations and overexpression of Ron induce transformation, tumor formation, and metastasis. Oncogene 20:6142–6151PubMedCrossRef

11.

Kretschmann KL, Eyob H, Buys SS, Welm AL (2010) The macrophage stimulating protein/Ron pathway as a potential therapeutic target to impede multiple mechanisms involved in breast cancer progression. Curr Drug Targets 11:1157–1168PubMedCrossRef

12.

Welm AL, Sneddon JB, Taylor C, Nuyten DS, van de Vijver MJ, Hasegawa BH, Bishop JM (2007) The macrophage-stimulating protein pathway promotes metastasis in a mouse model for breast cancer and predicts poor prognosis in humans. Proc Natl Acad Sci U S A 104:7570–7575PubMedCrossRef

13.

Kakiuchi S, Daigo Y, Tsunoda T, Yano S, Sone S, Nakamura Y (2003) Genome-wide analysis of organ-preferential metastasis of human small cell lung cancer in mice. Mol Cancer Res 1:485–499PubMed

14.

Kiura K, Watarai S, Shibayama T, Ohnoshi T, Kimura I, Yasuda T (1993) Inhibitory effects of cholera toxin on in vitro growth of human lung cancer cell lines. Anticancer Drug Des 8:417–428PubMed

15.

Otsuka S, Hanibuchi M, Ikuta K, Yano S, Goto H, Ogino H, Yamada T, Kakiuchi S, Nishioka Y, Takahashi T, Sone S (2009) A bone metastasis model with osteolytic and osteoblastic properties of human lung cancer ACC-LC-319/bone2 in natural killer cell-depleted severe combined immunodeficient mice. Oncol Res 17:581–591PubMedCrossRef

16.

Morita S, Kojima T, Kitamura T (2000) Plat-E: an efficient and stable system for transient packaging of retroviruses. Gene Ther 7:1063–1066PubMedCrossRef

17.

Tanaka T, Kitamura F, Nagasaka Y, Kuida K, Suwa H, Miyasaka M (1993) Selective long-term elimination of natural killer cells in vivo by an anti-interleukin-2 receptor β chain monoclonal antibody in mice. J Exp Med 178:1103–1107PubMedCrossRef

18.

Yano S, Zhang H, Hanibuchi M, Miki T, Goto H, Uehara H, Sone S (2003) Combined therapy with a new bisphosphonate, minodronate (YM529), and chemotherapy for multiple organ metastases of small cell lung cancer cells in severe combined immunodeficient mice. Clin Cancer Res 9:5380–5385PubMed

19.

Green LM, Reade JL, Ware CF (1984) Rapid colometric assay for cell viability: application to the quantitation of cytotoxic and growth inhibitory lymphokines. J Immunol Methods 70:257–268PubMedCrossRef

20.

Yano S, Nishioka Y, Izumi K, Tsuruo T, Tanaka T, Miyasaka M, Sone S (1996) Novel metastasis model of human lung cancer in SCID mice depleted of NK cells. Int J Cancer 67:211–217PubMedCrossRef

21.

Miki T, Yano S, Hanibuchi M, Sone S (2000) Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice. Oncol Res 12:209–217PubMed

22.

Willett CG, Wang MH, Emanuel RL, Graham SA, Smith DI, Shridhar V, Sugarbaker DJ, Sunday ME (1998) Macrophage-stimulating protein and its receptor in non-small-cell lung tumors: induction of receptor tyrosine phosphorylation and cell migration. Am J Respir Cell Mol Biol 18:489–496PubMed

23.

Kawaguchi M, Orikawa H, Baba T, Fukushima T, Kataoka H (2009) Hepatocyte growth factor activator is a serum activator of single-chain precursor macrophage-stimulating protein. FEBS J 13:3481–3490CrossRef

24.

Liotta LA, Kohn EC (2001) The microenvironment of the tumor-host interface. Nature 411:375–379PubMedCrossRef

25.

Fidler IJ (2002) The organ microenvironment and cancer metastasis. Differentiation 70:498–505PubMedCrossRef

26.

Takanami I, Takeuchi K, Kodaira S (1999) Tumor-associated macrophage infiltration in pulmonary adenocarcinoma: association with angiogenesis and poor prognosis. Oncology 57:138–142PubMedCrossRef

27.

Wagh PK, Peace BE, Waltz SE (2008) Met-related receptor tyrosine kinase Ron in tumor growth and metastasis. Adv Cancer Res 100:1–33PubMedCrossRef

28.

Iida I, Johkura K, Teng R, Kubota S, Cui L, Zhao X, Ogiwara N, Okouchi Y, Asanuma K, Nakayama J, Sasaki K (2003) Immunohistochemical localization of hepatocyte growth factor activator (HGFA) in developing mouse liver tissues. Heterogeneous distribution of HGFA protein. J Histochem Cytochem 9:1139–1149CrossRef

29.

Nanashima A, Shibata K, Nakayama T, Tobinaga S, Araki M, Kunizaki M, Takeshita H, Hidaka S, Sawai T, Nagayasu T, Yasutake T (2009) Clinical significance of microvessel count in patients with metastatic liver cancer originating from colorectal carcinoma. Ann Surg Oncol 16:2130–2137PubMedCrossRef

30.

van der Wal GE, Gouw AS, Kamps JA, Moorlag HE, Bulthuis ML, Molema G, de Jong KP (2012) Angiogenesis in synchronous and metachronous colorectal liver metastases: the liver as a permissive soil. Ann Surg 255:86–94PubMedCrossRef

31.

Gabr AG, Goto H, Hanibuchi M, Ogawa H, Kuramoto T, Suzuki M, Saijo A, Kakiuchi S, Trung VT, Sakaguchi S, Moriya Y, Sone S, Nishioka Y (2012) Erlotinib prevents experimental metastases of human small cell lung cancer cells with no epidermal growth factor receptor expression. Clin Exp Metastasis (in press)

32.

Wang D, Shen Q, Chen YQ, Wang MH (2004) Collaborative activities of macrophage-stimulating protein and transforming growth factor-β1 in induction of epithelial to mesenchymal transition: roles of the RON receptor tyrosine kinase. Oncogene 23:1668–1680PubMedCrossRef

33.

Lee WY, Chen HH, Chow NH, Su WC, Lin PW, Guo HR (2005) Prognostic significance of co-expression of RON and MET receptors in node-negative breast cancer patients. Clin Cancer Res 11:2222–2228PubMedCrossRef

34.

Kanteti R, Krishnaswamy S, Catenacci D, Tan YH, El-Hashani E, Cervantes G, Husain AN, Tretiakova M, Vokes EE, Huet H, Salgia R (2012) Differential expression of RON in small and non-small cell lung cancers. Genes Chromosomes Cancer 51:841–851PubMedCrossRef

35.

O’Toole JM, Rabenau KE, Burns K, Lu D, Mangalampalli V, Balderes P, Covino N, Bassi R, Prewett M, Gottfredsen KJ, Thobe MN, Cheng Y, Li Y, Hicklin DJ, Zhu Z, Waltz SE, Hayman MJ, Ludwig DL, Pereira DS (2006) Therapeutic implications of a human neutralizing antibody to the macrophage-stimulating protein receptor tyrosine kinase (RON), a c-MET family member. Cancer Res 66:9162–9170PubMedCrossRef

Title: Macrophage stimulating protein promotes liver metastases of small cell lung cancer cells by affecting the organ microenvironment
Authors: Seidai Sato
Masaki Hanibuchi
Takuya Kuramoto
Nodoka Yamamori
Hisatsugu Goto
Hirohisa Ogawa
Atsushi Mitsuhashi
Trung The Van
Soji Kakiuchi
Shin-ichi Akiyama
Yasuhiko Nishioka
Saburo Sone
Publication date: 01-03-2013
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 3/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-012-9540-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2013

The influence of neural cell adhesion molecule isoform 140 on the metastasis of thyroid carcinoma

Tumor location and nature of lymphatic vessels are key determinants of cancer metastasis

S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells

Aberrant methylation and loss expression of RKIP is associated with tumor progression and poor prognosis in gastric cardia adenocarcinoma

Potentiation of tumor cell invasion by co-culture with monocytes accompanying enhanced production of matrix metalloproteinase and fibronectin

Spontaneous metastasis in congenic mice with transgenic breast cancer is unaffected by plasminogen gene ablation

Keynote webinar | Spotlight on antibody–drug conjugates in cancer