Monoclonal antibodies against autocrine motility factor suppress gastric cancer

Jung,Hahn‑Sun; Lee,Su  In; Kang,Seung‑Hoon; Wang,Jin  Sang; Yang,Eun  Hee; Jeon,Byungwook; Myung,Jayhyuk; Baek,Ji  Young; Park,Song‑Kyu

doi:10.3892/ol.2017.6037

Monoclonal antibodies against autocrine motility factor suppress gastric cancer

Authors:
- Hahn‑Sun Jung
- Su In Lee
- Seung‑Hoon Kang
- Jin Sang Wang
- Eun Hee Yang
- Byungwook Jeon
- Jayhyuk Myung
- Ji Young Baek
- Song‑Kyu Park
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Affiliations: Boryung Central Research Institute, Boryung Pharmaceutical Co. Ltd., Ansan‑Si, Kyeongki‑Do 03127, Republic of Korea, College of Pharmacy, Republic of Korea University, Sejong 30019, Republic of Korea
Published online on: April 13, 2017 https://doi.org/10.3892/ol.2017.6037
Pages: 4925-4932

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Abstract

Autocrine motility factor (AMF), which is a secreted form of phosphoglucose isomerase, is mainly secreted by various tumors and has cytokine‑like activity. AMF is known to stimulate proliferation, survival and metastasis of cancer cells, and angiogenesis within a tumor. The present study investigated whether inhibition of AMF using targeted-antibodies was able to suppress the growth of cancer. A migration assay using a Boyden chamber was utilized to measure the activity of AMF on the motility of cancer cells. A recombinant human AMF (rhAMF) prepared from E. coli transformed with the pET22b‑AMF vector increased the motility of MDA‑MB‑231 and A549 cells, but it did not affect that of NCI‑N87 or HepG2 cells, which exhibited the ability to secrete high amounts of their own endogenous AMF into the culture medium. The extent to which the AMF receptor was expressed on cancer cells did not correlate clearly with the cell motility stimulated by rhAMF. In A549‑xenografted nude mice treated with sunitinib or cetuximab, a decrease in the plasma AMF concentration was accompanied by a reduction in tumor weight, suggesting an association between the plasma AMF concentration and anticancer activity. A monoclonal antibody (9A‑4H), which revealed a high binding affinity for E. coli-derived rhAMF, significantly suppressed the growth of tumors in Balb/c nude mice transplanted with the human gastric cancer cell line NCI‑N87, to the similar extent as trastuzumab, an anticancer antibody. The present study suggests, for the first time, that an antibody specific to AMF may be a therapeutic agent for gastric cancer.

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1	Liotta LA, Mandler R, Murano G, Katz DA, Gordon RK, Chiang PK and Schiffmann E: Tumor cell autocrine motility factor. Proc Natl Acad Sci USA. 83:pp. 3302–3306. 1986; View Article : Google Scholar : PubMed/NCBI
2	Gurney ME, Apatoff BR, Spear GT, Baumel MJ, Antel JP, Bania MB and Reder AT: Neuroleukin: A lymphokine product of lectin-stimulated T cells. Science. 234:574–581. 1986. View Article : Google Scholar : PubMed/NCBI
3	Xu W, Seiter K, Feldman E, Ahmed T and Chiao JW: The differentiation and maturation mediator for human myeloid leukemia cells shares homology with neuroleukin or phosphoglucose isomerase. Blood. 87:4502–4506. 1996.PubMed/NCBI
4	Cao MJ, Osatomi K, Matsuda R, Ohkubo M, Hara K and Ishihara T: Purification of a novel serine proteinase inhibitor from the skeletal muscle of white croaker (Argyrosomus argentatus). Biochem Biophys Res Commun. 272:485–489. 2000. View Article : Google Scholar : PubMed/NCBI
5	Yakirevich E and Naot Y: Cloning of a glucose phosphate isomerase/neuroleukin-like sperm antigen involved in sperm agglutination. Biol Reprod. 62:1016–1023. 2000. View Article : Google Scholar : PubMed/NCBI
6	Gomm SA, Keevil BG, Thatcher N, Hasleton PS and Swindell RS: The value of tumour markers in lung cancer. Br J Cancer. 58:797–804. 1988. View Article : Google Scholar : PubMed/NCBI
7	Baumann M, Kappl A, Lang T, Brand K, Siegfried W and Paterok E: The diagnostic validity of the serum tumor marker phosphohexose isomerase (PHI) in patients with gastrointestinal, kidney, and breast cancer. Cancer Invest. 8:351–356. 1990. View Article : Google Scholar : PubMed/NCBI
8	Tsutsumi S, Yanagawa T, Shimura T, Fukumori T, Hogan V, Kuwano H and Raz A: Regulation of cell proliferation by autocrine motility factor/phosphoglucose isomerase signaling. J Biol Chem. 278:32165–32172. 2003. View Article : Google Scholar : PubMed/NCBI
9	Tsutsumi S, Hogan V, Nabi IR and Raz A: Overexpression of the autocrine motility factor/phosphoglucose isomerase induces transformation and survival of NIH-3T3 fibroblasts. Cancer Res. 63:242–249. 2003.PubMed/NCBI
10	Haga A, Funasaka T, Deyashiki Y and Raz A: Autocrine motility factor stimulates the invasiveness of malignant cells as well as up-regulation of matrix metalloproteinase-3 expression via a MAPK pathway. FEBS Lett. 582:1877–1882. 2008. View Article : Google Scholar : PubMed/NCBI
11	Tsutsumi S, Yanagawa T, Shimura T, Kuwano H and Raz A: Autocrine motility factor signaling enhances pancreatic cancer metastasis. Clin Cancer Res. 10:7775–7784. 2004. View Article : Google Scholar : PubMed/NCBI
12	Funasaka T, Haga A, Raz A and Nagase H: Tumor autocrine motility factor is an angiogenic factor that stimulates endothelial cell motility. Biochem Biophys Res Commun. 285:118–128. 2001. View Article : Google Scholar : PubMed/NCBI
13	Silletti S, Watanabe H, Hogan V, Nabi IR and Raz A: Purification of B16-F1 melanoma autocrine motility factor and its receptor. Cancer Res. 51:3507–3511. 1991.PubMed/NCBI
14	Kanbe K, Chigira M and Watanabe H: Effects of protein kinase inhibitors on the cell motility stimulated by autocrine motility factor. Biochim Biophys Acta. 1222:395–399. 1994. View Article : Google Scholar : PubMed/NCBI
15	Tsutsumi S, Gupta SK, Hogan V, Collard JG and Raz A: Activation of small GTPase Rho is required for autocrine motility factor signaling. Cancer Res. 62:4484–4490. 2002.PubMed/NCBI
16	Chiu CG, St-Pierre P, Nabi IR and Wiseman SM: Autocrine motility factor receptor: A clinical review. Expert Rev Anticancer Ther. 8:207–217. 2008. View Article : Google Scholar : PubMed/NCBI
17	Kho DH, Zhang T, Balan V, Wang Y, Ha SW, Xie Y and Raz A: Autocrine motility factor modulates EGF-mediated invasion signaling. Cancer Res. 74:2229–2237. 2014. View Article : Google Scholar : PubMed/NCBI
18	Funasaka T, Hu H, Yanagawa T, Hogan V and Raz A: Down-regulation of phosphoglucose isomerase/autocrine motility factor results in mesenchymal-to-epithelial transition of human lung fibrosarcoma cells. Cancer Res. 67:4236–4243. 2007. View Article : Google Scholar : PubMed/NCBI
19	Niinaka Y, Harada K, Fujimuro M, Oda M, Haga A, Hosoki M, Uzawa N, Arai N, Yamaguchi S, Yamashiro M and Raz A: Silencing of autocrine motility factor induces mesenchymal-to-epithelial transition and suppression of osteosarcoma pulmonary metastasis. Cancer Res. 70:9483–9493. 2010. View Article : Google Scholar : PubMed/NCBI
20	Li Y, Che Q, Bian Y, Zhou Q, Jiang F, Tong H, Ke J, Wang K and Wan XP: Autocrine motility factor promotes epithelial-mesenchymal transition in endometrial cancer via MAPK signaling pathway. Int J Oncol. 47:1017–1024. 2015.PubMed/NCBI
21	Papaetis GS and Syrigos KN: Sunitinib: A multitargeted receptor tyrosine kinase inhibitor in the era of molecular cancer therapies. BioDrugs. 23:377–389. 2009. View Article : Google Scholar : PubMed/NCBI
22	Ciardiello F, de Vita F, Orditura M, Comunale D and Galizia G: Cetuximab in the treatment of colorectal cancer. Future Oncol. 1:173–181. 2005. View Article : Google Scholar : PubMed/NCBI
23	Hitt R, Martin P and Hidalgo M: Cetuximab in squamous cell carcinoma of the head and neck. Future Oncol. 2:449–457. 2006. View Article : Google Scholar : PubMed/NCBI
24	Iqbal N and Iqbal N: Imatinib: A breakthrough of targeted therapy in cancer. Chemother Res Pract. 2014:3570272014.PubMed/NCBI
25	Braghiroli MI, Sabbaga J and Hoff PM: Bevacizumab: Overview of the literature. Expert Rev Anticancer Ther. 12:567–580. 2012. View Article : Google Scholar : PubMed/NCBI
26	Holohan C, van Schaeybroeck S, Longley DB and Johnston PG: Cancer drug resistance: An evolving paradigm. Nat Rev Cancer. 13:714–726. 2013. View Article : Google Scholar : PubMed/NCBI
27	Takanami I, Takeuchi K, Watanabe H, Yanagawa T, Takagishi K and Raz A: Significance of autocrine motility factor receptor gene expression as a prognostic factor in non-small-cell lung cancer. Int J Cancer. 95:384–387. 2001. View Article : Google Scholar : PubMed/NCBI
28	Ohta Y, Tanaka Y, Hara T, Oda M, Watanabe S, Shimizu J and Watanabe Y: Clinicopathological and biological assessment of lung cancers with pleural dissemination. Ann Thorac Surg. 69:1025–1029. 2000. View Article : Google Scholar : PubMed/NCBI
29	Funasaka T and Raz A: The role of autocrine motility factor in tumor and tumor microenvironment. Cancer Metastasis Rev. 26:725–735. 2007. View Article : Google Scholar : PubMed/NCBI
30	Nabi IR, Watanabe H and Raz A: Identification of B16-F1 melanoma autocrine motility-like factor receptor. Cancer research. 50:409–414. 1990.PubMed/NCBI
31	Bang YJ, van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet. 376:687–697. 2010. View Article : Google Scholar : PubMed/NCBI
32	Kho DH, Nangia-Makker P, Balan V, Hogan V, Tait L, Wang Y and Raz A: Autocrine motility factor promotes HER2 cleavage and signaling in breast cancer cells. Cancer Res. 73:1411–1419. 2013. View Article : Google Scholar : PubMed/NCBI