Reconstruction of functionally normal and malignant human breast tissues in mice.

Proceedings of the National Academy of Sciences of the United States of America, 2004

826 citations recorded by the source corpus.

The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.

Subfields: Cancer Research, Oncology

View Paper: https://www.semanticscholar.org/paper/c18c38a95ff7ae5d752dd7dbf869016047c1383a

Citations in the corpus

• PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. (2009, neutral): “TGF-b1 and HGF have been also implicated in the tumorpromoting effects of TAFs (Bhowmick et al., 2004; Kuperwasser et al., 2004).”
• Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin signaling (2009, neutral): “NOD/SCID mice (n = 24) were used for mammary fat pad transplantation studies (Kuperwasser et al., 2004).”
• Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. (2006, neutral): “irradiated (4 Gy) fibroblasts as previously described (12), following”
• Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment. (2006, neutral): “Recently, several groups demonstrated the involvement of microenvironmental factors in tumor progression and proposed that the microenvironment may promote (Bhowmick et al., 2004; Kuperwasser et al., 2004) or suppress (Bissell et al.”
• Cancer stem cells: impact, heterogeneity, and uncertainty. (2012, neutral): “Mouse tissues differ from human tissues in terms of architecture and stromal cells (Kuperwasser et al., 2004).”
• A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. (2006, neutral): “…not ''contaminated'' with normal epithelial or stromal cells so that the clusters resolve more clearly in the cell lines, or that the differences are due to the absence of stromal or physiological interactions and/or signaling in cell culture (Kuperwasser et al., 2004; Radisky and Bissell, 2004).”
• Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. (2013, neutral): “Diagram indicating the genesis of the PDX models from patients with primary and advanced breast cancer, using two different implantation techniques (human in mouse [Kuperwasser et al., 2004] and simple orthotopic).”
• Tumor microenvironment: The role of the tumor stroma in cancer (2007, neutral): “The most widely studied to date are the fibroblasts, immune cells, and the vascular cells, which we will focus on in this review.”
• ALDH1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer (2009, neutral): “SUM149 was grown in adherent conditions using the recommended culture medium (26).”
• Therapeutic targeting of the tumor microenvironment. (2005, neutral): “…et al., 2001; Petersen et al., 1992; Schmeichel and Bissell, 2003), and the recent development of a “humanized” mammary gland xenograft model (Kuperwasser et al., 2004), allow human epithelial cells and stromal cells to be studied in vitro and in vivo, and are important advances in iden­…”
• Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state (2011, positive): “We used the humanized mouse mammary fat pad reconstitution assay (20) to test for human stem cell activity by assessing a cell’s ability to generate mammary structures in a humanizedmurine fat pad of NOD/SCID mice.”