Mediastinal lymph node metastasis model by orthotopic intrapulmonary implantation of Lewis lung carcinoma cells in mice

Doki, Yoshinori; Murakami, Kazuhiro; Yamaura, Takeshi; Sugiyama, Shigeki; Misaki, Takuro; Saiki, Ikuo

doi:10.1038/sj.bjc.6690178

Cited by 80 publications

(72 citation statements)

References 17 publications

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“…11 In brief, the left chest of anesthetized mice was incised 5 mm, and 20 ll aliquots of an LLC suspension (2 3 10 3 cells) admixed with 20 lg of Matrigel TM basement membrane matrix (BD Biosciences, San Jose, CA) were injected into the left lung parenchyma through the intercostal space. Mice were killed 15 days after implantation, and the weight of the tumors was measured.…”

Section: Tumor Proliferation In Vivomentioning

confidence: 99%

Severe pulmonary metastasis in obese and diabetic mice

Mori

Sakurai

Choo

et al. 2006

Intl Journal of Cancer

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Although obesity is known as a risk factor for several human cancers, the association of obesity with cancer recurrence and metastasis remains to be characterized. Here, B16-BL6 melanoma and Lewis lung carcinoma cells were intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number of experimental lung colonies was markedly promoted in these mice when compared with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable when cells were inoculated orthotopically. The use of B16-BL6 cells stably transfected with the luciferase gene revealed that the increased metastasis reflected a difference mainly within 6 hr after the intravenous inoculation of tumor cells. Administration of recombinant leptin in ob/ob mice abolished the increase in metastasis early on as well as the decrease in the splenic NK cell number. In addition, depletion of NK cells by an anti-asialo-GM1 antibody abrogated the enhanced metastasis in db/db mice. These results demonstrate that metastasis is markedly promoted in diabetic and obese mice mainly because of decreased NK cell function during the early phase of metastasis. ' 2006 Wiley-Liss, Inc.Key words: obesity; metastasis; NK cell; leptin Obesity has become one of the most critical problems in human health, because it can lead to more serious disorders such as cardiovascular disease, pulmonary disorders and metabolic syndrome. 1 Attention has recently been focused on the influence of obesity on carcinogenesis and the progression of cancer. A cohort study in the United States revealed that an increased body-mass index is significantly associated with higher rates of death because of cancer. 2 In addition, obesity increases the risk of cancer developing in the prostate, colorectum, breast, endometrium and elsewhere. [3][4][5][6][7] Similarly, the risk of renal cell cancer is increased in patients with diabetes mellitus, a disease closely associated with obesity. 8 These observations are well correlated with the finding that the carcinogen-induced multiplicity of premalignant colonic lesions is increased in db/db obese and diabetic mice. 9 Metastasis is the major cause of mortality in cancer patients. Maehle et al. reported that breast cancer patients with obesity had a higher risk of lymph node metastases. 10 Although evidence has accumulated of an association of cancer with obesity, the influence of obesity and diabetes on cancer metastasis remains to be investigated. In addition, the mechanisms by which obesity promotes the development and progression of cancer are still unknown. Material and methods MiceMale C57BL/6, C57BL/KsJ-db/db (db/db) and C57BL/6J-ob/ob (ob/ob) mice, 5-6 weeks old, were maintained in a specific pathogen-free barrier facility under laminar airflow conditions with a 12-hr light/dark cycle, a controlled humidity of 55% 6 5% and a temperature of 22°C 6 1°C. This study was conducted in accordance with the standards outlined in the Guidelines for the Care and Use of Laboratory Animals of the University of Toyama. Cell cultureB16-BL6 ...

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Section: Tumor Proliferation In Vivomentioning

confidence: 99%

Severe pulmonary metastasis in obese and diabetic mice

Mori

Sakurai

Choo

et al. 2006

Intl Journal of Cancer

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“…10,11 Other orthotopic athymic mouse models have also been reported for human cancers such as colon, pancreas, lung, stomach, liver, kidney, ovary, prostate, urinary bladder, breast, and head and neck. [12][13][14][15][16][17][18][19][20][21] Thus, an orthotopic athymic animal model would seem to be the most useful for studying esophageal cancer cell invasion and metastasis. No such model, however, has previously been reported.…”

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confidence: 99%

A novel orthotopic implantation model of human esophageal carcinoma in nude rats: CD44H mediates cancer cell invasionin vitro andin vivo

et al. 2001

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A new orthotopic esophageal cancer model was developed by implanting fragments of xenografts of T.T human esophageal squamous carcinoma cells into the cervical esophagus of athymic rats. The rats had symptoms analogous to the human clinical course such as respiratory distress, dysphagia, vomiting of blood, or Horner syndrome, followed by death resulting from suffocation. Microscopic metastases of lymph node were observed around the tumor in 3 of 18 rats. A new cell line (T.T-1) was established from these metastases. Flow cytometry showed that T.T-1 and T.T parental cells had nearly the same surface levels of ␤1-integrin, ␣2-integrin, ␣3-integrin and E-cadherin, and no expression of CD44v3, CD44v6 and ␣5-integrin. T.T-1 cells had a higher level of CD44H, however, and a greater binding efficiency to the extracellular matrix components; laminin, type IV collagen, hyaluronic acid, and fibronectin than T. Key words: esophageal cancer; orthotopic implantation; CD44; adhesion; invasionEsophageal cancer is one of the most lethal cancers. By the time it is diagnosed it is often at an advanced stage that is characterized by lymph node metastases and invasion to adjacent organs. Distant lymph node metastasis appears relatively early in patients with esophageal cancer because of anatomical characteristics that more lymphatic vessels run longitudinally than horizontally in the esophageal submucosal layer. Direct invasion of esophageal tumor cells into adjacent organs, especially the trachea or aorta, makes a complete resection impossible. The 5-year survival is around 30% to 50%, even after a complete resection with lymph node dissection. [1][2][3][4][5] Other treatment strategies such as chemoradiotherapy have not been definitely demonstrated to have curative effectiveness. 6,7 It seems, therefore, that an important preclinical goal is to elucidate the mechanisms involved in the invasion and metastasis of esophageal cancer cells and to search for novel treatment strategies in vivo.Most athymic animal models of human cancers have been produced by subcutaneous transplantations. Tumor cells rarely metastasize in these types of models, 8 even when highly aggressive tumors have served as the source of xenografts. 9 Several athymic mouse models of human pancreatic cancer using orthotopic implantation have resulted in invasive local tumor growth and subsequent lymph node and hepatic metastases. 10,11 Other orthotopic athymic mouse models have also been reported for human cancers such as colon, pancreas, lung, stomach, liver, kidney, ovary, prostate, urinary bladder, breast, and head and neck. 12-21 Thus, an orthotopic athymic animal model would seem to be the most useful for studying esophageal cancer cell invasion and metastasis. No such model, however, has previously been reported. Our present study was undertaken to develop this type of model. We have successfully produced transplants of xenografts of T.T human esophageal squamous cell carcinoma cells onto the esophagus of athymic rats. A new tumor cell line was developed from...

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“…Previous studies have showed that the biological behavior of cancer cells is influenced by the implantation organ (1), while properties of the immune system are also known to be different in each organ. A useful model for a solitary pulmonary tumor has previously been established by the intrapulmonary implantation of LLC cells in syngeneic immunocompetent mice (7,(19)(20)(21). This model has the advantage of being simple and easy regarding the implantation procedure with a small skin incision at a pre-determined site followed by direct puncturing through the intercostal space to the lung parenchyma, without thoracotomy or intubation.…”

Section: Discussionmentioning

confidence: 99%

Antitumor immune activity by chemokine CX3CL1 in an orthotopic implantation of lung cancer model in vivo

Kee

Arita

Shinohara

et al. 2012

Molecular and Clinical Oncology

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Abstract. Due to their chemoattractant properties stimulating the accumulation of infiltrating immune cells in tumors, chemokines are known to have antitumor effects. Fractalkine, a unique CX3C chemokine, is expressed in activated endothelial cells, while its receptor, CX3CR1, is expressed in cytolytic immune cells, such as natural killer cells, monocytes and some CD8 + T cells. The biological properties of cancer cells are affected by the implantation organ and differences in immune systems, requiring cancer implantation in orthotopic organs in an in vivo experiment. To develop new therapy strategies for lung cancer, an animal model reflecting the clinical features of lung cancer was previously established. This study aimed to determine whether CX3CL1-induced biological functions should be used for immune cell-based gene therapy of lung cancer in the orthotopic implantation model. An orthotopic intrapulmonary implantation of CX3CL1-stable expression in mouse lung cancer (LLC-CX3CL1) was performed to analyze growth. Results showed a significant decrease in tumor growth in the lung compared to the control cells (LLC-mock). Furthermore, the antitumor effects of CX3CL1 were derived from natural killer cell activities in the depletion experiment in vivo. Therefore, CX3CL1 has the potential of a useful therapeutic target in lung cancer.

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Mediastinal lymph node metastasis model by orthotopic intrapulmonary implantation of Lewis lung carcinoma cells in mice

Cited by 80 publications

References 17 publications

Severe pulmonary metastasis in obese and diabetic mice

Severe pulmonary metastasis in obese and diabetic mice

A novel orthotopic implantation model of human esophageal carcinoma in nude rats: CD44H mediates cancer cell invasionin vitro andin vivo

Antitumor immune activity by chemokine CX3CL1 in an orthotopic implantation of lung cancer model in vivo

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