Artificial lymphogenous metastatic model using orthotopic implantation of human lung cancer

Ishikura, Hisashi; Kondo, Kazuya; Miyoshi, Takanori; Kinoshita, Hidetaka; Hirose, Toshiyuki; Monden, Yasumasa

doi:10.1016/s0003-4975(00)01144-9

Cited by 12 publications

(20 citation statements)

References 13 publications

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“…(18,26,27) In an intrapulmonary model, tumor growth in the lung was found microscopically at day 7 after implantation. In contrast, micrometastasis to the mediastinum was observed on day 5.…”

Section: Discussionmentioning

confidence: 99%

“…It was considered that the tumor grew in an artificial environment produced by the high pressure of the tumor cell injection. (26) Matrigel is a basement membrane matrix preparation extracted from Engelbreth-Holm-Swarm mouse sarcoma. Matrigel was used frequently in the implantation of tumor cells into the pleural cavity to fix tumor cells to the site of injection and reduce operation motility.…”

Section: Discussionmentioning

confidence: 99%

“…(18-20,26 -27) However, studies have shown that coinjection with Matrigel enhances the local tumor growth rate, while increasing the drug resistance of the lung cancer cell lines. (26,28) EDTA is used frequently for tissue culture and is not expensive. Simultaneous administration of EDTA resulted in 80 -100% tumor formation rate but did not cause damage to tumor-bearing normal tissue and did not affect tumor distribution histologically (Tables 1,2; Figs 3,4).…”

Section: Discussionmentioning

confidence: 99%

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Development of an orthotopic transplantation model in nude mice that simulates the clinical features of human lung cancer

Kang¹,

Omura²,

Suzuki³

et al. 2006

Cancer Science

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The objective of the present study was to establish an orthotopic tumor transplantation model in nude mice that closely resembles the clinical features of human lung cancer. The human lung adenocarcinoma A549 cell line and the squamous cell carcinoma SQ5 cell line were used. Tumor cells suspended in serum-free medium were injected directly into the main bronchi of anesthetized female Balb/c athymic nude mice (7-9 weeks old) with or without simultaneous administration of 0.01 M ethylenediaminetetracetic acid (EDTA). In some experiments, lung carcinoma cells harvested from tumors transplanted subcutaneously were recultured and used for intratracheal implantation. Tumor nodules that formed in the lung were counted and confirmed by histological examination. Administration of A549 cells with EDTA resulted in a 70% engraftment rate (n = 10). Recultured A549 cells without and with EDTA resulted in 20% (n = 5) and 80% (n = 5) engraftment rates, respectively. Administration of SQ5 cells without or with EDTA formed 50% (n = 4) and 67% (n = 6) engraftment rates, respectively. Recultured (1) In Japan, lung cancer caused 12.7% of cancer-related mortalities in women and 22% of cancer-related mortalities in men in 2001. (2) In addition, no more than 14.9% of patients survived after treatment for lung cancer. It is a general consensus that the poor prognosis of patients with lung cancer reflects the aggressive biological nature of the cancer as well as the ineffectiveness of early detection procedures and treatment.Efforts have been made to develop effective treatments for lung cancer using an in vivo model. For example, an orthotopic transplantation model of human small-cell lung carcinoma (SCLC) demonstrates sensitivity to cisplatin and resistance to mitomycin C, reflecting the clinical situation. In contrast, the same tumor xenograft implanted subcutaneously responded to mitomycin C and not to cisplatin, thus failing to match the clinical behavior of SCLC.(3) Organ microenvironment may influence the phenotype and sensitivity to chemotherapeutics of tumor cells, as described originally by Pagets' 'seed and soil' theory (4) and confirmed by others.(5,6) Therefore, it is essential to establish a clinically relevant in vivo model that simulates the clinical features for lung cancer research.Several orthotopic transplantation models of lung cancer have been developed in rodents. Examples include direct implantation of human cancerous tissue (7) and injection of tumor cells into the rodent airway, (8,9) pleural cavity, (10,11) or lung parenchyma after skin incision (12) or thoracotomy. (13,14) However, the complex technique for performing transplantation in these models limited their widespread use. Most of the research and development of novel diagnostics and therapeutics for lung cancer still rely on subcutaneous tumor models, which are potentially less clinically relevant.In the present study, we developed a new orthotopic transplantation human lung cancer model in athymic nude mice using a reproducible technique. The presen...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of an orthotopic transplantation model in nude mice that simulates the clinical features of human lung cancer

Kang¹,

Omura²,

Suzuki³

et al. 2006

Cancer Science

View full text Add to dashboard Cite

show abstract

“…Orthotopic Intrapulmonary Implantation Procedure As in our previous studies (15,16,19), the mice were anesthetized by ether inhalation. A 1-cm transverse incision was made in the left lateral thorax in the right lateral decubitus position.…”

Section: Antimetastatic Efficacy Of Mmi-166 In Lung Cancer Modelmentioning

confidence: 99%

“…The purpose of this study was to evaluate the effects of MMI-166 on both the growth of the implanted tumor and the lymph node metastasis of the mediastinum using an orthotopically implanted severe combined immunodeficiency (SCID) mouse model of the Ma44-3 lung cancer cell line (15,16).…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer

Fujino¹,

Kondo²,

Ishikura³

et al. 2005

Molecular Cancer Therapeutics

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Matrix metalloproteinases (MMP) are considered to be critically involved in tumor invasion and the metastasis of various cancers. MMI-166 is a selective inhibitor of matrix metalloproteinase (MMP-2, MMP-9, and MMP-14). The purpose of this study was to evaluate the effects of MMI-166 on both the growth of the implanted tumor and the lymph node metastasis of the mediastinum and prolonging the life span, using an orthotopic implantation model of the Ma44-3 cancer cell line. We examined the anti-invasive effect of MMI-166 in lung cancer cell lines using an in vitro invasion assay. Next, we examined the anticancer effect of MMI-166 in vivo. MMI-166 (200 mg/kg body weight) or a vehicle was administered orally to the orthotopically implanted lung cancer model. MMI-166 dose-dependently inhibited the invasion of cancer cell lines with expressions of MMP-2 and/or MMP-9 in vitro. In vivo, MMI-166 significantly inhibited mediastinal lymph node metastasis in this orthotopic model (weight of the mediastinum: control, 0.089 F 0.009 versus MMI-166, 0.069 F 0.008 mg; P = 0.005; metastatic area: control, 93,495 F 55,747 versus MMI-166, 22,747 F 17,478 pixels; P = 0.045). MMI-166 prolonged the life span by 6 days in median survival time in the orthotopically implanted model (P = 0.039). These results showed that MMI-166 could possibly inhibit lymph node metastasis and prolong the life span in lung cancer patients. [Mol Cancer Ther 2005; 4(9):1409 -16]

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Animal models and molecular imaging tools to investigate lymph node metastases

et al. 2011

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Lymph node metastasis is a strong predictor of poor outcome in cancer patients. Animal studies of lymph node metastasis are constrained by difficulties in the establishment of appropriate animal models, limitations in the noninvasive monitoring of lymph node metastasis progression, and challenges in the pathologic confirmation of lymph node metastases. In this comprehensive review, we summarize available preclinical animal cancer models for noninvasive imaging and identification of lymph node metastases of non-hematogenous cancers. Furthermore, we discuss the strengths and weaknesses of common noninvasive imaging modalities used to identify tumor-bearing lymph nodes and provide guidelines for their pathological confirmation.

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Artificial lymphogenous metastatic model using orthotopic implantation of human lung cancer

Cited by 12 publications

References 13 publications

Development of an orthotopic transplantation model in nude mice that simulates the clinical features of human lung cancer

Development of an orthotopic transplantation model in nude mice that simulates the clinical features of human lung cancer

Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer

Animal models and molecular imaging tools to investigate lymph node metastases

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