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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Small cell and non small cell lung cancer form metastasis on cellular 4D lung model

Authors: Dhruva K. Mishra, Ross A. Miller, Kristi A. Pence, Min P. Kim

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Metastasis is the main cause of death for lung cancer patients. The ex vivo 4D acellular lung model has been shown to mimic this metastatic process. However, the main concern is the model’s lack of cellular components of the tumor’s microenvironment. In this study, we aim to determine if the intact lung microenvironment will still allow lung cancer metastasis to form.

Methods

We harvested a heart-lung block from a rat and placed it in a bioreactor after cannulating the pulmonary artery, trachea and tying the right main bronchus for 10–15 days without any tumor cells as a control group or with NSCLC (A549, H1299 or H460), SCLC (H69, H446 or SHP77) or breast cancer cell lines (MCF7 or MDAMB231) through the trachea. We performed lobectomy, H&E staining and IHC for human mitochondria to determine the primary tumor’s growth and formation of metastatic lesions. In addition, we isolated circulating tumor cells (CTC) from the model seeded with GFP tagged cells.

Results

In the control group, no gross tumor nodules were found, H&E staining showed hyperplastic cells and IHC showed no staining for human mitochondria. All of the models seeded with cancer cell lines formed gross primary tumor nodules that had microscopic characteristics of human cancer cells on H&E staining with IHC showing staining for human mitochondria. CTC were isolated for those cells labeled with GFP and they were viable in culture. Finally, all cell lines formed metastatic lesions with cells stained for human mitochondria.

Conclusion

The cellular ex vivo 4D model shows that human cancer cells can form a primary tumor, CTC and metastatic lesions in an intact cellular environment. This study suggests that the natural matrix scaffold is the only necessary component to drive metastatic progression and that cellular components play a role in modulating tumor progression.
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Literature
1.
2.
Mishra DK, Creighton CJ, Zhang Y, Chen F, Thrall MJ, Kim MP. Ex vivo four-dimensional lung cancer model mimics metastasis. Ann Thorac Surg. 2015;99(4):1149–56.CrossRefPubMedPubMedCentral
3.
Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, Ikonomou L, Kotton D, Vacanti JP. Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med. 2010;16(8):927–33.CrossRefPubMed
4.
Petersen TH, Calle EA, Colehour MB, Niklason LE. Matrix composition and mechanics of Decellularized lung scaffolds. Cells Tissues Organs. 2012;195(3):222–31.
5.
Kuttan R, Spall RD, Duhamel RC, Sipes IG, Meezan E, Brendel K. Preparation and composition of alveolar extracellular matrix and incorporated basement membrane. Lung. 1981;159(6):333–45.CrossRefPubMed
6.
Mishra DK, Thrall MJ, Baird BN, Ott HC, Blackmon SH, Kurie JM, Kim MP. Human lung cancer cells grown on acellular rat lung matrix create perfusable tumor nodules. Ann Thorac Surg. 2012;93(4):1075–81.CrossRefPubMedPubMedCentral
7.
Mishra DK, Sakamoto JH, Thrall MJ, Baird BN, Blackmon SH, Ferrari M, Kurie JM, Kim MP. Human lung cancer cells grown in an ex vivo 3D lung model produce matrix metalloproteinases not produced in 2D culture. PLoS One. 2012;7(9):e45308.CrossRefPubMedPubMedCentral
8.
Mishra DK, Scott KL, Wardwell-Ozgo JM, Thrall MJ, Kim MP. Circulating tumor cells from 4D model have less integrin beta 4 expression. J Surg Res. 2015;193(2):745–53.CrossRefPubMed
9.
Vishnoi M, Mishra DK, Thrall MJ, Kurie JM, Kim MP. Circulating tumor cells from a 4-dimensional lung cancer model are resistant to cisplatin. J Thorac Cardiovasc Surg. 2014;148(3):1056–63. discussion 1063-4CrossRefPubMed
10.
Mishra DK, Compean SD, Thrall MJ, Liu X, Massarelli E, Kurie JM, Kim MP. Human lung fibroblasts inhibit non-small cell lung Cancer metastasis in ex vivo 4D model. Ann Thorac Surg. 2015;100(4):1167–74. discussion 1174CrossRefPubMed
11.
12.
13.
Bissell MJ, Hines WC. Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med. 2011;17(3):320–9.CrossRefPubMedPubMedCentral
14.
15.
Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer. 2009;9(4):239–52.CrossRefPubMed
16.
Francia G, Cruz-Munoz W, Man S, Xu P, Kerbel RS. Mouse models of advanced spontaneous metastasis for experimental therapeutics. Nat Rev Cancer. 2011;11(2):135–41.CrossRefPubMedPubMedCentral
17.
Yuan J, Knorr J, Altmannsberger M, Goeckenjan G, Ahr A, Scharl A, Strebhardt K. Expression of p16 and lack of pRB in primary small cell lung cancer. J Pathol. 1999;189(3):358–62.CrossRefPubMed
18.
Pence KA, Mishra DK, Thrall M, Dave B, Kim MP. Breast cancer cells form primary tumors on ex vivo four-dimensional lung model. J Surg Res. 2017;210:181-187.
Metadata
Title
Small cell and non small cell lung cancer form metastasis on cellular 4D lung model
Authors
Dhruva K. Mishra
Ross A. Miller
Kristi A. Pence
Min P. Kim
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/s12885-018-4358-x

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