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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Evaluation of metastatic niches in distant organs after surgical removal of tumor-bearing lymph nodes

Authors: Jinhua Zheng, Limin Jia, Shiro Mori, Tetsuya Kodama

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Surgical removal of primary tumors can promote the incidence of tumor metastasis. However, molecular mechanisms underlying this process remain unclear.

Methods

We inoculated tumor cells expressing luciferase gene  into subiliac lymph node (SiLN) of the MXH10/Mo-lpr/lpr mice. The tumor-bearing SiLNs were surgically removed at a certain period of time after inoculation.

Results

In vivo bioluminescence imaging system and histological staining revealed metastasis in lung, proper axillary lymph node (PALN) and liver. The lung metastasis rate in SiLN removal groups was significantly higher than in the control group using Fisher exact test. Mann-Whitney U-test indicated that the luciferase-positive tumor cells in the lung and liver were significantly higher than in the control groups. The lung samples in SiLN removal groups had strong expression of lysine oxidase (LOX). Moreover, the number of CD11b+ cells in the lung and liver in the SiLN removal groups was significantly increased, which was positively correlated with LOX expression level. In addition, the condition of LOX and CD11b in liver was similar to lung. In the SiLN surgical removal groups, the matrix metalloproteinase (MMP)-2 and VEGFA expression in the lung tissues was significantly higher than in the control groups; the collagen fibers per area around the pulmonary vessels was quite significantly lower and negatively correlated with the expression of MMP-2 by Spearman’s analysis. Our data indicated that the reticular fibers were deposited and disordered in the tumor tissues of the lungs in the removal groups, and the reticular fibers per area was higher than in the control groups. The tumor cells in the PALN of control groups were significantly higher than in the SiLN removal groups, and CD169+ and CD11c+ cells were also higher than in the SiLN removal groups.

Conclusions

Altogether, surgical removal of the tumor-bearing lymph node promoted tumor metastasis through changing the niche in lung and liver. Treatment targeting the metastatic niche might be an effective strategy to prevent tumor metastasis, thereby possibly increasing the survival and reducing the incidence of metastasis in cancer patients.
Literature
1.
Zhang Y, Zhang N, Hoffman RM, Zhao M. Surgically-induced multi-organ metastasis in an Orthotopic syngeneic Imageable model of 4T1 murine breast Cancer. Anticancer Res. 2015;35:4641–6.PubMed
2.
Lee SY, Jeong EK, Ju MK, Jeon HM, Kim MY, Kim CH, et al. induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation. Mol Cancer. 2017;16:10.CrossRefPubMedPubMedCentral
3.
Kerbel RS. A decade of experience in developing preclinical models of advanced- or early-stage spontaneous metastasis to study antiangiogenic drugs, metronomic chemotherapy, and the tumor microenvironment. Cancer J. 2015;21:274–83.CrossRefPubMed
4.
Tang Z, Zhou X, Lin Z, Yang B, Ma Z, Ye S, et al. Surgical treatment of hepatocellular carcinoma and related basic research with special reference to recurrence and metastasis. Chin Med J. 1999;112:887–91.PubMed
5.
6.
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820–7.CrossRefPubMedPubMedCentral
7.
Sceneay J, Smyth MJ, Moller A. The pre-metastatic niche: finding common ground. Cancer Metastasis Rev. 2013;32:449–64.CrossRefPubMed
8.
Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30:668–81.CrossRefPubMed
9.
Demicheli R, Retsky MW, Hrushesky WJ, Baum M. Tumor dormancy and surgery-driven interruption of dormancy in breast cancer: learning from failures. Nat Clin Pract Oncol. 2007;4:699–710.CrossRefPubMed
10.
Tagliabue E, Agresti R, Carcangiu ML, Ghirelli C, Morelli D, Campiglio M, et al. Role of HER2 in wound-induced breast carcinoma proliferation. Lancet. 2003;362:527–33.CrossRefPubMed
11.
Maniwa Y, Okada M, Ishii N, Kiyooka K. Vascular endothelial growth factor increased by pulmonary surgery accelerates the growth of micrometastases in metastatic lung cancer. Chest. 1998;114:1668–75.CrossRefPubMed
12.
Sano D, Gule MK, Rosenthal DI, Bell D, Yates J, El-Naggar AK, et al. Early postoperative epidermal growth factor receptor inhibition: safety and effectiveness in inhibiting microscopic residual of oral squamous cell carcinoma in vivo. Head Neck. 2013;35:321–8.CrossRefPubMed
13.
Fisher B. Laboratory and Clinical research in breast cancer--a personal adventure: the David a. Karnofsky memorial lecture. Cancer Res. 1980;40:3863–74.PubMed
14.
Shao L, Ouchi T, Sakamoto M, Mori S, Kodama T. Activation of latent metastases in the lung after resection of a metastatic lymph node in a lymph node metastasis mouse model. Biochem Biophys Res Commun. 2015;460:543–8.CrossRefPubMed
15.
Shao L, Mori S, Yagishita Y, Okuno T, Hatakeyama Y, Sato T, et al. Lymphatic mapping of mice with systemic lymphoproliferative disorder: usefulness as an inter-lymph node metastasis model of cancer. J Immunol Methods. 2013;389:69–78.CrossRefPubMed
16.
Miura Y, Mikada M, Ouchi T, Horie S, Takeda K, Yamaki T, et al. Early diagnosis of lymph node metastasis: importance of intranodal pressures. Cancer Sci. 2016;107:224–32.CrossRefPubMedPubMedCentral
17.
Li L, Mori S, Kodama M, Sakamoto M, Takahashi S, Kodama T. Enhanced sonographic imaging to diagnose lymph node metastasis: importance of blood vessel volume and density. Cancer Res. 2013;73:2082–92.CrossRefPubMed
18.
Ishii T, Ishii T. On the preparation of argyrophilic fibers (a modification of the Bielschowsky-Maresch silver impregnation method). Mikroskopie. 1965;20:1–11.PubMed
19.
Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A, et al. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell. 2009;15:35–44.CrossRefPubMedPubMedCentral
20.
21.
Watson DI. Abdominal wall metastasis after laparoscopic gastroenterostomy. Med J Aust. 1995;163:106–7.PubMed
22.
Tsuchiya Y, Sawada S, Yoshioka I, Ohashi Y, Matsuo M, Harimaya Y, et al. Increased surgical stress promotes tumor metastasis. Surgery. 2003;133:547–55.CrossRefPubMed
23.
Hofer SO, Shrayer D, Reichner JS, Hoekstra HJ, Wanebo HJ. Wound-induced tumor progression: a probable role in recurrence after tumor resection. Arch Surg. 1998;133:383–9.CrossRefPubMed
24.
Camphausen K, Moses MA, Beecken WD, Khan MK, Folkman J, O'Reilly MS. Radiation therapy to a primary tumor accelerates metastatic growth in mice. Cancer Res. 2001;61:2207–11.PubMed
25.
Gorski DH, Beckett MA, Jaskowiak NT, Calvin DP, Mauceri HJ, Salloum RM, et al. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. 1999;59:3374–8.PubMed
26.
Melsens E, Verberckmoes B, Rosseel N, Vanhove C, Descamps B, Pattyn P, et al. The VEGFR inhibitor Cediranib improves the efficacy of fractionated radiotherapy in a colorectal Cancer xenograft model. Eur Surg Res. 2017;58:95–108.CrossRefPubMed
27.
Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009;15:220–31.CrossRefPubMedPubMedCentral
28.
29.
Rucci N, Sanita P, Angelucci A. Roles of metalloproteases in metastatic niche. Curr Mol Med. 2011;11:609–22.CrossRefPubMed
30.
Sangaletti S, Tripodo C, Santangelo A, Castioni N, Portararo P, Gulino A, et al. Mesenchymal transition of high-grade breast carcinomas depends on extracellular matrix control of myeloid suppressor cell activity. Cell Rep. 2016;17:233–48.CrossRefPubMed
31.
32.
Sceneay J, Chow MT, Chen A, Halse HM, Wong CS, Andrews DM, et al. Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. Cancer Res. 2012;72:3906–11.CrossRefPubMed
33.
34.
Asano K, Nabeyama A, Miyake Y, Qiu CH, Kurita A, Tomura M, et al. CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity. 2011;34:85–95.CrossRefPubMed
35.
Dhondt B, Rousseau Q, De Wever O, Hendrix A. Function of extracellular vesicle-associated miRNAs in metastasis. Cell Tissue Res. 2016;365:621–41.CrossRefPubMed
36.
Ma X, Sheng S, Wu J, Jiang Y, Gao X, Cen X, et al. LncRNAs as an intermediate in HPV16 promoting myeloid-derived suppressor cell recruitment of head and neck squamous cell carcinoma. Oncotarget. 2017;8(26):42061–75.CrossRefPubMedPubMedCentral
37.
Cao MX, Jiang YP, Tang YL, Liang XH. The crosstalk between lncRNA and microRNA in cancer metastasis: orchestrating the epithelial-mesenchymal plasticity. Oncotarget. 2017;8:12472–83.PubMed
38.
El Gazzar M. microRNAs as potential regulators of myeloid-derived suppressor cell expansion. Innate Immun. 2014;20:227–38.CrossRefPubMed
39.
Jayawardana K, Schramm SJ, Tembe V, Mueller S, Thompson JF, Scolyer RA, et al. Identification, review, and systematic cross-validation of microRNA prognostic signatures in metastatic melanoma. J Invest Dermatol. 2016;136:245–54.CrossRefPubMed
Metadata
Title
Evaluation of metastatic niches in distant organs after surgical removal of tumor-bearing lymph nodes
Authors
Jinhua Zheng
Limin Jia
Shiro Mori
Tetsuya Kodama
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4538-8

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