A new in vivo model for studying invasion and metastasis of esophageal squamous cell carcinoma

Furihata, Tadashi; Sakai, Tomoya; Kawamata, Hitoshi; Omotehara, Fumie; Shinagawa, Yasuhiro; Imura, Johji; Ueda, Yoshihiko; Kubota, Keiichi; Fujimori, Takahiro

doi:10.3892/ijo.19.5.903

Cited by 16 publications

(21 citation statements)

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“…A model of squamous cell carcinoma of the cervical esophagus in rats achieved 99.5% tumor take with 3 lymphatic micrometastases in 22 rats 37. In an inoculation model of squamous cell carcinoma of the esophagus, metastasis was not detectable, although primary tumor growth was substantial 38…”

Section: Discussionmentioning

confidence: 97%

Complementary use of fluorescence and magnetic resonance imaging of metastatic esophageal cancer in a novel orthotopic mouse model

Gros

Dohrmann

Peldschus

et al. 2010

Intl Journal of Cancer

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We describe the development of an aggressive orthotopic metastatic model of esophageal cancer, which is visualized in real time with combined magnetic resonance imaging (MRI) and fluorescence imaging. The aim of the study was to describe the development of a novel model of metastatic tumor disease of esophageal carcinoma and use this model to evaluate fluorescence and MRI in early detection of local and metastatic disease. The human esophageal adenocarcinoma cell line PT1590 was stably transfected with green fluorescent protein (GFP). Nude mice were orthotopically implanted with PT1590-GFP cells. Orthotopic tumor growth as well as metastatic spread was examined by fluorescence imaging and high-resolution MRI at defined intervals after orthotopic implantation. Highly aggressive novel fluorescent cell lines were isolated from metastatic tissues and put into culture. After implantation of these cells, 100% of the animals developed orthotopic primary tumors. In 83% of animals, metastatic spread to liver, lung and lymph nodes was observed. Primary tumor growth could be visualized with fluorescence imaging and with MRI with high correlation between the 2 methods. Fluorescence imaging allows fast, sensitive, and economical imaging of the primary and metastatic tumor without anesthesia. With MRI, anatomical structures are visualized more precisely and tumors can be more accurately localized to specific organs. This model should prove highly useful to understand esophageal carcinoma and to identify novel therapeutics for this treatment-resistant disease.Esophageal carcinoma is one of the most common cancers in the world and, especially in the advanced stages, a leading cause of death. In the early stages, surgical resection is the only successful treatment. Survival is, however, mostly related to lymph node or distant organ metastases, and there is no effective therapeutic target for successfully treating metastasis. Therefore, understanding metastatic pathways and developing treatment options to reduce the size of the primary tumor and to treat or prevent metastatic spread is of greatest importance.Orthotopic models made by implanting histologically intact human tumor tissue into mice develop the local and metastatic behaviours occurring in human patients. 1-4 However, a metastatic orthotopic model of esophageal adenocarcinoma, which resembles the aggressive behavior in human disease, has not been established. Lack of such a model has been an impediment for the discovery and development of effective therapeutics for metastatic esophageal cancer.In addition, accurate and reproducible tumor imaging of orthotopic models can monitor the efficacy of novel therapeutics in real time. Multiple imaging techniques have been applied to small animal imaging. Previously, computed tomography, abdominal ultrasound and magnetic resonance imaging (MRI) have been used. A variety of newer imaging modalities such as in vivo fluorescence and bioluminescence imaging have now been established. [1][2][3][4] In addition, highresolution MRI with...

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Section: Discussionmentioning

confidence: 97%

Complementary use of fluorescence and magnetic resonance imaging of metastatic esophageal cancer in a novel orthotopic mouse model

Gros

Dohrmann

Peldschus

et al. 2010

Intl Journal of Cancer

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“…The poor prognosis of esophageal cancer is due in large part to the early-stage invasion and metastases to adjacent tissue and distant organs [3]. Therefore, disrupting invasion and metastasis is essential to develop effective therapies and treatments for esophageal cancer.…”

Section: Introductionmentioning

confidence: 99%

TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression

Zhou

Ran

et al. 2008

Clin Exp Metastasis

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Esophageal cancer is characterized by rapid clinical progression and poor prognosis due to adjacent tissue invasion and distant organs metastasis at a very early stage. TM4SF3 (transmembrane 4 superfamily 3), a member of tetraspanin family, has been reported as a metastasis associated gene in many types of tumors. Herein, we described new properties of TM4SF3 in tumor metastasis, which suggested that this gene might be involved in esophageal carcinoma metastasis. Western blotting revealed that TM4SF3 was overexpressed in 57.1% (8/14) of esophageal carcinomas and esophageal carcinoma cell lines with high-invasive potential. Exogenous expression of TM4SF3 in two low-invasive esophageal carcinoma cell lines, KYSE150 and EC9706, significantly promoted cell migration and invasion. Upregulating TM4SF3 expression in EC9706 cells promoted xenograft tumor invading into surrounding tissues, enhanced lung metastasis, and shortened the lifespan of mice (median survival EC9706-TM4SF3 106.5 days versus EC9706-Vector 169.0 days, P < 0.0001) in a spontaneous metastasis model. Further studies demonstrated that ADAM12m was upregulated by TM4SF3 overexpression in vitro and in vivo. Abrogating up-expression of ADAM12m by siRNA significantly suppressed TM4SF3-mediated invasion. Together, these data from our studies indicated that overexpression of TM4SF3 in esophageal cancer conferred advantage to the invasion and metastasis of this destructive disease. Upregulated expression of ADAM12m by TM4SF3 might play a key role in TM4SF3-mediated invasion and metastasis. TM4SF3 and ADAM12m might be potential targets of esophageal carcinoma for anti-metastasis therapy.

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“…11,12) We first clarified in detail the molecular and genetic characteristics of a human non-metastasizing esophageal SCC cell line, T.Tn, 12) and then developed an orthotopic inoculation model for esophageal cancer cells in nude mice. 11) In the present study, we isolated a metastasizing subclone from the parental non-metastasizing T.Tn cell line by in vitro selection and by the use of a nude mouse orthotopic inoculation model. Then, we compared the expression profiles of 9206 genes in the parental T.Tn cells and the metastasizing subclone by cDNA microarray analysis, and identified several genes differentially expressed in the metastasizing subclone.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Identification of genes differentially expressed in a newly isolated human metastasizing esophageal cancer cell line, T.Tn‐AT1, by cDNA microarray

et al. 2003

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sophageal squamous cell carcinoma (SCC) is one of the most aggressive cancers. Esophageal SCC is relatively common in countries in Eastern Asia, such as China and Japan, and is characterized by poor prognosis and rapid clinical progression, with a high frequency of lymph node metastasis and recurrence. The 5-year survival rate of patients with esophageal SCC showing submucosal invasion is low (40-75%) 1-5) compared with that for patients with colon cancer (over 80%). 4,5) In addition, lymph node metastasis is commonly found in esophageal SCC, even when the tumor invades only the submucosa. Lymph node metastasis is the main cause of the poor prognosis for the patients with esophageal SCC.Consequently, the identification of the genes associated with metastasis of esophageal SCC is very important. Microarray analysis has been used to investigate the gene expression profiles of esophageal SCC tissues and esophageal cancer cell lines with various characteristics.6-10) When clinical materials are used for microarray analysis, it might be necessary to look at the overall expression profiles of genes (if possible) by clustering analysis in the different pathological stages, such as dysplasia, carcinoma in situ, and invasive cancer with or without metastasis. However, to isolate gene(s) related to metastasis, it would be convenient to use cell lines with different metastatic potentials derived from the same parental cells, and a reliable model system is therefore required for examining the metastatic potential of cancer cells.In our previous experiments, we established in vitro and in vivo model systems for studying invasion and metastasis of esophageal SCC cells. 11,12) We first clarified in detail the molecular and genetic characteristics of a human non-metastasizing esophageal SCC cell line, T.Tn, 12) and then developed an orthotopic inoculation model for esophageal cancer cells in nude mice.11) In the present study, we isolated a metastasizing subclone from the parental non-metastasizing T.Tn cell line by in vitro selection and by the use of a nude mouse orthotopic inoculation model. Then, we compared the expression profiles of 9206 genes in the parental T.Tn cells and the metastasizing subclone by cDNA microarray analysis, and identified several genes differentially expressed in the metastasizing subclone. Materials and MethodsCell line. A human esophageal SCC cell line, T.Tn 13) was obtained from JCRB (Japanese Collection of Research Bioresources, Osaka). T.Tn cells were grown in 1:1 mixture of Dulbecco's modified Eagle's medium (Nissui, Tokyo) and F-12 (Life Technologies, Inc., Gaithersburg, MD) supplemented with 10% fetal calf serum (FCS; Sigma, St. Louis, MO), 100 µg/ml streptomycin, 100 units/ml penicillin (Life Technologies, Inc.), and 0.25 µg/ml amphotericin B (Life Technologies, Inc.) in a humidified atmosphere of 95% air and 5% CO 2 at 37°C. HT1080 cells are derived from a human fibrosarcoma cell line known to secrete a large amount of several matrix-degrading enzymes (purchased from Dai-Nippon Seiyaku, Osa...

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A new in vivo model for studying invasion and metastasis of esophageal squamous cell carcinoma

Cited by 16 publications

References 0 publications

Complementary use of fluorescence and magnetic resonance imaging of metastatic esophageal cancer in a novel orthotopic mouse model

Complementary use of fluorescence and magnetic resonance imaging of metastatic esophageal cancer in a novel orthotopic mouse model

TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression

Identification of genes differentially expressed in a newly isolated human metastasizing esophageal cancer cell line, T.Tn‐AT1, by cDNA microarray

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