Growth of Human Tumor Xenografts Implanted under the Renal Capsule of Normal Immunocompetent Mice

Bogdén, Arthur E.; Haskell, Paula M.; LePage, Doreen; Kelton, Diane; Cobb, William R.; Esber, Henry J.

doi:10.1159/000162947

Cited by 88 publications

(62 citation statements)

References 6 publications

(6 reference statements)

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“…Of the various graft sites available, the subrenal capsular (SRC) site offers the particular advantage of very high organ perfusion and potentially rapid development of graft microvasculature (8). In spite of this, SRC grafting of human tumor tissue has been plagued by poor tumor take rates for a number of decades.…”

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confidence: 99%

Establishment in Severe Combined Immunodeficiency Mice of Subrenal Capsule Xenografts and Transplantable Tumor Lines from a Variety of Primary Human Lung Cancers: Potential Models for Studying Tumor Progression–Related Changes

Cutz

Guan²,

Bayani³

et al. 2006

Clinical Cancer Research

105

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Purpose: Lung cancer is a biologically diverse disease and relevant models reflecting its diversity would facilitate the improvement of existing therapies. With a view to establishing such models, we developed and evaluated xenografts of a variety of human lung cancers. Experimental Design: Using nonobese diabetic/severe combined immunodeficiency mice, subrenal capsule xenografts were generated from primary lung cancer tissue, including moderately and poorly differentiated squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, large cell undifferentiated carcinoma, and carcinosarcoma. After 4 to 12 weeks, xenografts were harvested for serial transplantation and comparison with the original tissue via histologic, chromosomal, and cytogenetic analyses. Results: Xenografts were successfully established. H&E staining showed that xenografts retained major histologic features of the original cancers. Immunohistochemistry and fluorescence in situ hybridization confirmed the human origin of the tumor cells and development in xenografts of murine supportive stroma. Four transplantable lines were developed from rapidly growing tumors (>5 generations), i.e., a small cell lung carcinoma, large cell undifferentiated carcinoma, pulmonary carcinosarcoma, and squamous cell carcinoma. Analyses including spectral karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization, revealed that the xenografts were genetically similar to the original tumors, showing chromosomal abnormalities consistent with karyotypic changes reported for lung cancer. Conclusions: The subrenal capsule xenograft approach essentially provides a living tumor bank derived from patient material and a means for isolating and expanding specific cell populations. The transplantable tumor lines seem to provide good models for studying various aspects of tumor progression and a platform for developing novel therapeutic regimens, with the possibility of patient-tailored therapies.

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confidence: 99%

Establishment in Severe Combined Immunodeficiency Mice of Subrenal Capsule Xenografts and Transplantable Tumor Lines from a Variety of Primary Human Lung Cancers: Potential Models for Studying Tumor Progression–Related Changes

Cutz

Guan²,

Bayani³

et al. 2006

Clinical Cancer Research

105

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“…Following established methods (32)(33)(34), the IGROV-1 tumor cell line was tested for growth in vivo in a subrenal capsule assay. Ten million cells were mixed with 300 g of fibrinogen in PBS, pH 7.4, and 0.16 units of thrombin in double-strength DMEM and incubated at 37°C for 15 min.…”

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confidence: 99%

Tissue-engineered cells producing complex recombinant proteins inhibit ovarian cancer in vivo

Stephen

Masiakos

Segev

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…After SC turnout implantation, a fibrous capsule surrounding the tumour is seen as part of the reaction of the host animal [3], while local immune factors also play a role in initiating or inhibiting the metastatic cascade. The SRC assay was first described by Bogden [5,9,10], who used this method for testing the sensitivity of tumours of various origins to different chemotherapeutic agents. Following SRC implantation no fibrous capsule is formed by the animal [3] and the vascularization at the site of the implant seems to aid full expression of the metastatic ability of the cells [8].…”

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confidence: 99%

“…The technique described by Bogden et al [5] was used. Tumours were mechanically minced under a stereoscopic microscope in order to obtain fragments with average volume of approximately 0.…”

Section: Src Implantmentioning

confidence: 99%

Metastatic potential of human renal cell carcinoma: experimental model using subrenal capsule implantation in athymic nude mice

et al. 1992

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Summary. The aim of this study was to determine whether subrenal capsule (SRC) implantation is a suitable model for the study of the metastatic potential of our human renal cell carcinoma (HRCC) lines and to establish new sublines with enhanced metastatic ability. NMRI athymic nude mice 7-11 weeks old received SRC implantation of our HRCC lines RC43 and RC21. These lines were not metastatic when implanted s.c. Mice were killed after 4 or 8 weeks, or when moribund. With the RC43 cell line the success rate for implantation was 69 %, with 89% of these showing metastases. The average volume of the implanted tumour fragments was 0.5 mm 3 (range 0.28-0.7), the average volume at the primary site at the time of death was 9087 (9-32000) mm 3. Metastases were found in lymph nodes, liver, spleen, peritoneum, psoas muscle, pancreas, diaphragm and skin. The average volume of the metastases was 4139 (0.5-9000) mm 3. Growing cell lines were established in vivo and in vitro from one splenic, one peritoneal, one diaphragmatic, and one hepatic metastasis. These sublines have faster in vivo and slower in vitro growth rates than the parental lines. With the RC21 cell line the success rate for implantation was 56% and the metastatic rate 78%. The average volume of the implanted tumour was 0.8 mm 3 (0.28-1.2), the average volume at the primary site at the time of death was 2685 mm 3 (1.4-6534) and the average volume of metastases was 7.1 mm 3 (0.5-37.5). Metastases were found in lymph nodes, lung and skin. No establishment was attempted for RC21 because of the small dimensions of these metastases. SRC implantation is thus considered a useful tool for the study of the metastatic ability of our cell lines RC43 and RC21. The establishment of new sublines with a faster growth rate and an enhanced metastatic ability will be useful for further studies on the metastatic process. Key words: Metastatic potential -Subrenal capsule implantation -Human Renal Cell CarcinomaCancer patients rarely die of their primary tumours. Establishment of metastases in various organs and their subsequent growth usually cause the terminal cachexia of neoplastic patients.The non-random pattern of visceral metastases suggested to Paget [1] more than 100 years ago that the growth of metastases was due to an affinity between turnout cells (seeds) and a suitable environment in some organs (soil). Since then, the metastatic process has only been partially clarified, mainly because of the relative scarcity of experimental models that could reliably reproduce the interactions between host and tumour cells.Human renal cell carcinoma (HRCC) is an uncommon malignancy (6 % of all tumours diagnosed each year) with a poor prognosis ranging from 73 to 8 % survival at 5 years depending on the stage at diagnosis [2]. The establishment of HRCC lines growing in vitro or in vivo is not easy. In our laboratory only 10 % of implanted tumours produced a serially transplantable line [3]. Furthermore, the simple model of an s.c.-growing tumour is not very useful for research regarding ...

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Growth of Human Tumor Xenografts Implanted under the Renal Capsule of Normal Immunocompetent Mice

Cited by 88 publications

References 6 publications

Establishment in Severe Combined Immunodeficiency Mice of Subrenal Capsule Xenografts and Transplantable Tumor Lines from a Variety of Primary Human Lung Cancers: Potential Models for Studying Tumor Progression–Related Changes

Establishment in Severe Combined Immunodeficiency Mice of Subrenal Capsule Xenografts and Transplantable Tumor Lines from a Variety of Primary Human Lung Cancers: Potential Models for Studying Tumor Progression–Related Changes

Tissue-engineered cells producing complex recombinant proteins inhibit ovarian cancer in vivo

Metastatic potential of human renal cell carcinoma: experimental model using subrenal capsule implantation in athymic nude mice

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