Induction of multicellular 3‐D spheroids of MCF‐7 breast carcinoma cells by neutrophil‐derived cathepsin G and elastase

Cancer Science - Tập 96 Số 9 - Trang 560-570 - 2005
Satoru Yui1, Kazutaka Tomita1, Tomoya Kudo1, Shingo Ando1, Masatoshi Yamazaki1
1Faculty of Pharmaceutical Sciences, Teikyo University, 1091‐1 Sagamiko, Tsukui‐gun, Kanagawa 199‐0195, Japan

Tóm tắt

In tumor metastasis, multicellular aggregates of tumor cells form and disseminate into the blood or lymph vessels from the tumor mass, following the formation of tumor cell emboli in distant vessels. However, the mechanism by which aggregates form in the tumor mass is unknown. Neutrophils often exist in tumors and are considered to affect tumor development. We observed that neutrophils had the capacity to induce the aggregation of MCF‐7 human breast carcinoma cells adhering to culture substrates. When MCF‐7 cells were cultured with rat inflammatory neutrophils, the soluble fraction of their lysate, and the conditioned medium of neutrophils stimulated with N‐formyl‐Met‐Leu‐Phe plus cytochalasin B, multicellular aggregates formed within 16 h, and tightly aggregated 3‐D spheroids formed when the cultures were prolonged. The spheroid‐inducing reaction was reversible and energy‐dependent. The MCF‐7 cells induced to aggregate by the neutrophil extract showed growth potential, although the growth rate of the cells was slightly reduced. The aggregation was dependent on E‐cadherin, because the spheroids dispersed into isolated cells on incubation with EGTA or anti‐E‐cadherin antibody following pipetting. The aggregation‐inducing activity in neutrophils was completely inhibited by soybean trypsin‐chymotrypsin inhibitor. Moreover, the commercially available human neutrophil elastase and cathepsin G induced the aggregation of MCF‐7 cells and formation of spheroids. The proteases secreted by infiltrated neutrophils in tumors are implicated in the dissemination of tumor aggregates from primary tumor sites. (Cancer Sci 2005; 96: 560 –570)

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Tài liệu tham khảo

Nicholson GL, 1988, Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites, Biochim Biophys Acta, 948, 175

10.1016/S0092-8674(00)81470-1

10.1016/S0092-8674(00)81478-6

10.1016/0304-419X(94)90003-5

10.1016/S0002-9440(10)65575-7

10.1002/ijc.10329

10.1126/science.1067100

10.1016/S0304-419X(01)00038-5

10.1016/S0002-9440(10)61147-9

Tomlinson JS, 2001, An intact overexpressed E‐cadherin/α,β‐catenin axis characterizes the lymphovascular emboli of inflammatory breast carcinoma, Cancer Res, 61, 5231

10.1002/cncr.11332

10.1016/S0014-2964(73)80022-2

Liotta LA, 1976, The significance of hematogenous tumor cell clumps in the metastatic process, Cancer Res, 36, 889

Weiss L, 1988, Interactions of cancer cells with the microvasculature during metastasis, FASEB J, 2, 12, 10.1096/fasebj.2.1.3275560

10.1038/bjc.1990.339

10.1002/ijc.2910180310

10.1016/S0140-6736(00)04046-0

10.1023/A:1015587423262

Tsunawaki S, 1983, Mechanisms of lectin and antibody‐dependent polymorphonuclear leukocyte‐mediated cytolysis, Gann, 74, 265

Morikawa K, 1985, Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear β‐1,3‐D‐glucan and other immunomodulators in murine cells, Cancer Res, 45, 3482

10.1038/bjc.1989.70

10.1182/blood.V97.2.339

10.1158/0008-5472.CAN-03-1808

10.1248/bpb.26.753

10.1084/jem.181.1.435

10.1002/ijc.2910340417

10.1073/pnas.86.15.5859

10.1111/j.1349-7006.1991.tb01868.x

10.1016/S0002-9440(10)63580-8

10.1007/BF02623676

10.1080/09622935020138208

10.1016/0022-1759(83)90418-0

Nakajima K, 1979, Mapping the extended substrate binding site of cathepsin G and human leukocyte elastase, J Biol Chem, 254, 4027, 10.1016/S0021-9258(18)50690-6

10.1152/ajpcell.1997.273.4.C1109

10.1146/annurev.cb.08.110192.001515

Takeichi M, 1993, Dynamic control of cell–cell adhesion for multicellular organization, CR Acad Sci III, 316, 813

10.1002/jlb.59.5.716

Henson P, 1988, Inflammation. Basic Principles and Clinical Correlates, 363

10.1016/S0076-6879(76)45061-9

10.1016/0014-4827(58)90214-3

10.1038/sj.onc.1207181

10.1242/dev.102.4.639

10.1126/science.1065206

10.1023/A:1014594825502

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Cancer Science

Tập 96 Số 9

560-570

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