Heterogeneous Metastasis Efficiency of Isogenic Orthotopic Colon Cancer Xenografts Reveals Distinctive Gene Expression Profiles

Abal, Miguel; Fsihi, Hafida; Bras-Gonçalves, Rui; Doll, Andreas; Boyé, Karine; Janssen, Klaus–Peter; Alameda, Francesc; Reventós, Jaume; Louvard, Daniel; Magdelénat, H.; Poupon, Marie‐France; Robine, Sylvie

doi:10.1159/000103009

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…This will ideally improve the clinical treatment of endometrial cancer by pharmaceuticals, since invasion and metastasis are the major causes of death from cancer. 38 …”

Section: Discussionmentioning

confidence: 99%

An orthotopic endometrial cancer mouse model demonstrates a role for RUNX1 in distant metastasis

Doll

González

Abal

et al. 2009

Intl Journal of Cancer

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Endometrial carcinoma is the most common malignancy of the female genital tract in industrialized countries. Metastasis is the major cause of endometrial cancer deaths. Therefore, there is a vital need for clinically relevant in vivo models allowing the elucidation of the molecular and cellular mechanisms underlying metastatic behavior. In this study, we describe an innovative experimental orthotopic model of human endometrial carcinoma. Implantation in the bifurcation of the uterine horns resulted in tumors integrated into the myometrial compartment, which can be used and further exploited for the study of in vivo angiogenesis, myometrial invasion, and the metastatic capacity of endometrial cancer cells. This orthotopic model also represents a suitable tool to analyze how tumorigenesis and distant metastasis of endometrial cancer might be influenced by gene alteration, by modulating its expression in the original cancer cell line. One of the candidate genes implicated in endometrial cancer is the transcription factor RUNX1. The over-expression of RUNX1 in the endometrial cancer cell line HEC1A and the transplantation of these cells to the uterus of nude mice were associated specifically with distant metastasis in the lung. RUNX1 plays a role in the establishment of metastases in endometrial cancer. Translated to the clinics, these models would be equivalent to an advanced undifferentiated carcinoma with node affectation (stage IIIC) and distant metastasis (stage IVB). These patients would be candidates for adjuvant therapy, not efficient until today, and therefore, our models are actually suitable for the design and evaluation of experimental therapies. ' 2009 UICC

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“…This will ideally improve the clinical treatment of endometrial cancer by pharmaceuticals, since invasion and metastasis are the major causes of death from cancer. 38 …”

Section: Discussionmentioning

confidence: 99%

An orthotopic endometrial cancer mouse model demonstrates a role for RUNX1 in distant metastasis

Doll

González

Abal

et al. 2009

Intl Journal of Cancer

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“…Finally, we also present evidence of the utility of these models for the evaluation of how the process of metastasis is influenced by gene‐expression. This will ideally improve the clinical treatment of endometrial cancer by pharmaceuticals, since invasion and metastasis are the major causes of death from cancer 38…”

Section: Discussionmentioning

confidence: 99%

Rheological behavior and microstructure of bimodal suspensions of core‐shell structured swollen particles

Nakamura

Tachi

2006

J of Applied Polymer Sci

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ABSTRACT:The rheological behavior and microstructure of bimodal suspensions of core-shell structured swollen particles have been examined with changing volume ratio of two different sized particles. As the volume fraction of large particles increases, the viscosity, degree of shear-thinning, and the critical shear stress c decreases, while the interparticle distance of the microstructure increases. The suspensions exhibit single mode rheological behavior and have a single diffraction peak in the SAXS profiles. These results suggest that the bimodal suspensions of the core-shell structured swollen particles behave likely to unimodal suspensions of hard spheres with alloy like single mode microstructure composed of hypothetical intermediate size particle. The relationship between c and can be represented as c ϭ 3kT/4 3 , which corresponds to the dynamics of the Brownian hard sphere model with being the particle diameter. These findings indicate that the shear-thinning of the suspensions can be attributed to dynamical competition between the thermal motion and the hydrodynamic motion under shear flow and that the mechanism can be applied to bimodal suspensions of the swollen particles as well as unimodal suspensions of hard spheres.

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“…1) of metastasis suggests that the frequency of metastatic variants within a tumor determines metastatic potential (25). Further, metastatic variants may be unstable, resulting in a dynamic equilibrium between the generation and loss of cells with a metastatic phenotype (26).…”

Section: Cancer Researchmentioning

confidence: 99%

Clonal Selection of Metastasis within the Life History of a Tumor

Talmadge

2007

Cancer Research

110

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IntroductionTumor metastasis is a clonally selective process that occurs as part of tumor progression, a hypothesis supported by experimental and clinical research. Data supporting this hypothesis were first introduced by Fidler and Kripke in the late 1970s (1), providing a powerful model to gain insight into the mechanism(s) of metastasis. Studies of cellular genetic and epigenetic heterogeneity within tumors (1-3) support the selective process of metastasis, as have studies of clonal selection and cellular expansion following metastasis (4,5). In the original clonal selection studies (1), orthotopic tumor models were used because they faithfully reproduce clinical invasion, histopathology, cellular shedding, and metastasis (6), showing the clonal origin (1, 4) and selective mechanisms (7,8) of metastasis. Clonal Selection in the Process of MetastasisThe growth of a tumor focus at a site distant to the primary tumor represents the final step in the multistep process of metastasis, which has the potential to incorporate numerous selective events. Implicit to the clonal selection hypothesis (Fig. 1) is the presence within the primary tumor of at least one tumor population that expresses all of the up-regulated or inactivated genes required to successfully complete the metastatic process. As such, primary tumors may also have cellular subpopulations that express none or some of the characteristics required to complete the metastatic process. A corollary to the clonal selection hypothesis is the suggestion that individual metastases can originate from multiple clonal subpopulations that may have occurred within the primary tumor, resulting in biological diversity among metastatic foci. Thus, primary tumors can have multiple clonal subpopulations capable of forming metastatic foci, resulting in individual metastases expressing different phenotypes (5, 7). Further, due to the genetic instability (9), a clonal metastasis can rapidly become heterogeneous (5, 10). Although the clonal selection hypothesis was formally shown within rodent models in 1977 (1), it is confirmed daily by clinical pathologists. Histologic examination of primary tumors shows cellular heterogeneity based on morphology and expression of membrane receptors. For example, morphologically diverse areas can occur within a tumor such as foci of ductal carcinoma in situ within a primary breast carcinoma. Similarly, estrogen receptor, Her2/neu, or p53 expression varies between and within tumors and metastases, ranging from 1% to >90% of cells. Thus, clonal selection of metastases can result in phenotypically diverse metastases (intrahost heterogeneity), such that within the same patient some metastases can be positive whereas others are negative for a specific phenotype.Clonal selection and intrahost metastatic heterogeneity have strongly been supported by murine studies (4, 5, 7). However, clinical support has been less extensive due to experimental and methodologic challenges. Metastatic tissue may be obtained asynchronously, relative to primary tumor t...

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Heterogeneous Metastasis Efficiency of Isogenic Orthotopic Colon Cancer Xenografts Reveals Distinctive Gene Expression Profiles

Cited by 4 publications

References 34 publications

An orthotopic endometrial cancer mouse model demonstrates a role for RUNX1 in distant metastasis

An orthotopic endometrial cancer mouse model demonstrates a role for RUNX1 in distant metastasis

Rheological behavior and microstructure of bimodal suspensions of core‐shell structured swollen particles

Clonal Selection of Metastasis within the Life History of a Tumor

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