Increased complexity in carcinomas: Analyzing and modeling the interaction of human cancer cells with their microenvironment

被引:48
作者
Stadler, Mira [1 ]
Walter, Stefanie [1 ]
Walzl, Angelika [1 ]
Kramer, Nina [1 ]
Unger, Christine [1 ]
Scherzer, Martin [1 ]
Unterleuthner, Daniela [1 ]
Hengstschlaeger, Markus [1 ]
Krupitza, Georg [2 ]
Dolznig, Helmut [1 ]
机构
[1] Med Univ Vienna, Inst Med Genet, Wahringer Str 10, A-1090 Vienna, Austria
[2] Med Univ Vienna, Inst Pathol, A-1090 Vienna, Austria
关键词
Cancer heterogeneity; Tumor stroma; 3D; Spheroid; Drug development; LASER-CAPTURE MICRODISSECTION; MULTICELLULAR TUMOR SPHEROIDS; IMAGING MASS-SPECTROMETRY; EPITHELIAL-MESENCHYMAL TRANSITIONS; STEM-CELLS; IN-VITRO; COLORECTAL-CANCER; GENE-EXPRESSION; STROMAL FIBROBLASTS; DRUG-RESISTANCE;
D O I
10.1016/j.semcancer.2015.08.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Solid cancers are not simple accumulations of malignant tumor cells but rather represent complex organ-like structures. Despite a more chaotic general appearance as compared to the highly organized setup of healthy tissues, cancers still show highly differentiated structures and a close interaction with and dependency on the interwoven connective tissue. This complexity within cancers is not known in detail at the molecular level so far. The first part of this article will shortly describe the technology and strategies to quantify and dissect the heterogeneity in human solid cancers. Moreover, there is urgent need to better understand human cancer biology since the development of novel anti-cancer drugs is far from being efficient, predominantly due to the scarcity of predictive preclinical models. Hence, in vivo and in vitro models were developed, which better recapitulate the complexity of human cancers, by their intrinsic three-dimensional nature and the cellular heterogeneity and allow functional intervention for hypothesis testing. Therefore, in the second part 3D in vitro cancer models are presented that analyze and depict the heterogeneity in human cancers. Advantages and drawbacks of each model are highlighted and their suitability to preclinical drug testing is discussed. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:107 / 124
页数:18
相关论文
共 248 条
[61]   Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement [J].
Fischbach, Claudia ;
Kong, Hyun Joon ;
Hsiong, Susan X. ;
Evangelista, Marta B. ;
Yuen, Will ;
Mooney, David J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (02) :399-404
[62]  
FJELLBIRKELAND L, 1995, VIRCHOWS ARCH, V426, P169
[63]   An integrated computational/experimental model of tumor invasion [J].
Frieboes, HB ;
Zheng, X ;
Sun, CH ;
Tromberg, B ;
Gatenby, R ;
Cristini, V .
CANCER RESEARCH, 2006, 66 (03) :1597-1604
[64]   Organotypic Culture Model of Pancreatic Cancer Demonstrates that Stromal Cells Modulate E-Cadherin, β-Catenin, and Ezrin Expression in Tumor Cells [J].
Froeling, Fieke E. M. ;
Mirza, Tariq A. ;
Feakins, Roger M. ;
Seedhar, Angela ;
Elia, George ;
Hart, Ian R. ;
Kocher, Hemant M. .
AMERICAN JOURNAL OF PATHOLOGY, 2009, 175 (02) :636-648
[65]   Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells [J].
Gaggioli, Cedric ;
Hooper, Steven ;
Hidalgo-Carcedo, Cristina ;
Grosse, Robert ;
Marshall, John F. ;
Harrington, Kevin ;
Sahai, Erik .
NATURE CELL BIOLOGY, 2007, 9 (12) :1392-U92
[66]   The perivascular niche regulates breast tumour dormancy [J].
Ghajar, Cyrus M. ;
Peinado, Hector ;
Mori, Hidetoshi ;
Matei, Irina R. ;
Evason, Kimberley J. ;
Brazier, Helene ;
Almeida, Dena ;
Koller, Antonius ;
Hajjar, Katherine A. ;
Stainier, Didier Y. R. ;
Chen, Emily I. ;
Lyden, David ;
Bissell, Mina J. .
NATURE CELL BIOLOGY, 2013, 15 (07) :807-+
[67]   Effects of Scrophularia extracts on tumor cell proliferation, death and intravasation through lymphoendothelial cell barriers [J].
Giessrigl, Benedikt ;
Yazici, Gokhan ;
Teichmann, Mathias ;
Kopf, Sabine ;
Ghassemi, Sara ;
Atanasov, Atanas G. ;
Dirsch, Verena M. ;
Grusch, Michael ;
Jaeger, Walter ;
Ozmen, Ali ;
Krupitza, Georg .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2012, 40 (06) :2063-2074
[68]   Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (GEDI) and a prostate-specific antibody [J].
Gleghorn, Jason P. ;
Pratt, Erica D. ;
Denning, Denise ;
Liu, He ;
Bander, Neil H. ;
Tagawa, Scott T. ;
Nanus, David M. ;
Giannakakou, Paraskevi A. ;
Kirby, Brian J. .
LAB ON A CHIP, 2010, 10 (01) :27-29
[69]   AlgiMatrix™ Based 3D Cell Culture System as an In-Vitro Tumor Model for Anticancer Studies [J].
Godugu, Chandraiah ;
Patel, Apurva R. ;
Desai, Utkarsh ;
Andey, Terrick ;
Sams, Alexandria ;
Singh, Mandip .
PLOS ONE, 2013, 8 (01)
[70]   A method for preparation of hydrogel microcapsules for stem cell bioproces sing and stem cell therapy [J].
Goldshmid, Revital ;
Mironi-Harpaz, Iris ;
Shachaf, Yonatan ;
Seliktar, Dror .
METHODS, 2015, 84 :35-43