Tumor engineering: the other face of tissue engineering.

Advances in tissue engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function for a given tissue. We believe that the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of 'tumor engineering', that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physical scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment.

[1]  Nak Won Choi,et al.  Oxygen-controlled three-dimensional cultures to analyze tumor angiogenesis. , 2010, Tissue engineering. Part A.

[2]  Sindy K. Y. Tang,et al.  Paper-supported 3D cell culture for tissue-based bioassays , 2009, Proceedings of the National Academy of Sciences.

[3]  M J Bissell,et al.  Tumors are unique organs defined by abnormal signaling and context. , 2001, Seminars in cancer biology.

[4]  J Folkman,et al.  Transplacental carcinogenesis by stilbestrol. , 1971, The New England journal of medicine.

[5]  L. Coussens,et al.  CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. , 2009, Cancer cell.

[6]  D. Mooney,et al.  Polymeric system for dual growth factor delivery , 2001, Nature Biotechnology.

[7]  Mina J Bissell,et al.  Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments. , 2009, Integrative biology : quantitative biosciences from nano to macro.

[8]  J. Folkman Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[9]  D. Melton,et al.  Endothelial signaling during development , 2003, Nature Medicine.

[10]  Daniel A Fletcher,et al.  Tissue Geometry Determines Sites of Mammary Branching Morphogenesis in Organotypic Cultures , 2006, Science.

[11]  A. Kate Sasser,et al.  Mesenchymal Stem Cell Transition to Tumor-Associated Fibroblasts Contributes to Fibrovascular Network Expansion and Tumor Progression , 2009, PloS one.

[12]  S. Rafii,et al.  Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth , 2001, Nature Medicine.

[13]  John M L Ebos,et al.  Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. , 2009, Cancer cell.

[14]  M. Bissell The differentiated state of normal and malignant cells or how to define a "normal" cell in culture. , 1981, International review of cytology.

[15]  M. Sporn The war on cancer , 1996, The Lancet.

[16]  L. Ellis,et al.  Cancer: The nuances of therapy , 2009, Nature.

[17]  M J Bissell,et al.  How does the extracellular matrix direct gene expression? , 1982, Journal of theoretical biology.

[18]  J. Pollard,et al.  Macrophages regulate the angiogenic switch in a mouse model of breast cancer. , 2006, Cancer research.

[19]  Robert A. Weinberg,et al.  Comparative Biology of Mouse versus Human Cells: Modelling Human Cancer in Mice O P I N I O N , 2022 .

[20]  M J Bissell,et al.  Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. , 1996, Physiological reviews.

[21]  Mina J Bissell,et al.  Modeling dynamic reciprocity: engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation. , 2005, Seminars in cancer biology.

[22]  Jason P. Gleghorn,et al.  Microfluidic scaffolds for tissue engineering. , 2007, Nature materials.

[23]  Masahiro Inoue,et al.  Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. , 2009, Cancer cell.

[24]  H. Dvorak Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. , 1986, The New England journal of medicine.

[25]  F. Miller,et al.  Factors affecting growth and drug sensitivity of mouse mammary tumor lines in collagen gel cultures. , 1985, Cancer research.

[26]  Rakesh K. Jain,et al.  Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy , 2001, Nature Medicine.

[27]  J. Folkman,et al.  Is angiogenesis an organizing principle in biology and medicine? , 2007, Journal of pediatric surgery.

[28]  M. Bissell,et al.  The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells. , 1995, The Journal of clinical investigation.

[29]  D. Heber,et al.  Preadipocytes stimulate breast cancer cell growth. , 1998, Nutrition and cancer.

[30]  M. Sporn,et al.  Mediation of wound-related Rous sarcoma virus tumorigenesis by TGF-beta. , 1990, Science.

[31]  Mina J. Bissell,et al.  Putting tumours in context , 2001, Nature Reviews Cancer.

[32]  David J Mooney,et al.  Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement , 2009, Proceedings of the National Academy of Sciences.

[33]  David Roblin,et al.  Translational research in the pharmaceutical industry: from bench to bedside. , 2006, Drug discovery today.

[34]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[35]  Sophie Lelièvre,et al.  beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. , 2002, Cancer cell.

[36]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.

[37]  Kenneth M. Yamada,et al.  Modeling Tissue Morphogenesis and Cancer in 3D , 2007, Cell.

[38]  M. Bissell,et al.  Endothelial cell migration and vascular endothelial growth factor expression are the result of loss of breast tissue polarity. , 2009, Cancer research.

[39]  P. Hein,et al.  Carcinoma-associated fibroblasts stimulate tumor progression of initiated human epithelium , 2000, Breast Cancer Research.

[40]  D. Jukic A novel three-dimensional model to quantify metastatic melanoma invasion , 2008 .

[41]  Tobias Schmelzle,et al.  Engineering tumors with 3D scaffolds , 2007, Nature Methods.

[42]  Genee Y. Lee,et al.  The morphologies of breast cancer cell lines in three‐dimensional assays correlate with their profiles of gene expression , 2007, Molecular oncology.

[43]  Claudia Fischbach,et al.  Microfluidic culture models of tumor angiogenesis. , 2010, Tissue engineering. Part A.

[44]  Joe Tien,et al.  Formation of perfused, functional microvascular tubes in vitro. , 2006, Microvascular research.

[45]  M. Bissell,et al.  Epithelial to mesenchymal transition in human breast cancer can provide a nonmalignant stroma. , 2003, The American journal of pathology.

[46]  M. Bissell,et al.  Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Christopher Chiu,et al.  Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis , 2006, Proceedings of the National Academy of Sciences.