Playing tumor architect

Co-culture spheroids as new preclinical models for understanding tumor initiation and progression and developing therapies

Get ready for the next-generation of preclinical in vitro tumor models! Researchers have recently shown that co-cultures of tumor and stromal cells assembled into three-dimensional (3D) spheroids can provide better understanding of cancer therapeutics and facilitate establishment of improved pharmacokinetics, efficacy, and safety profiles.

Tumors are highly complex. They consist of multiple interacting cells populations organized in three-dimensional (3D) structures. Endothelial cells and other types of cells are recruited to form the tumor vasculature which provide oxygen and nutrient for the growing tumor mass. This important process has been largely ignored in existing preclinical in vitro tumor models, many of which are based on two-dimensional (2D) monolayer cell cultures, which do not capture the nutrient and oxygen gradients and the microenvironment reminiscent of the in vivo setting.

Upreti et al. have developed a preclinical in vitro model that can facilitate the intra/intercellular crosstalk and mimic the in vivo tumor and endothelial cell architecture. Their findings were published in the December 2011 issue of Translational Oncology. The researchers hypothesized that tumor cell biology and treatment response would be more informative when done in the presence of stromal components, like endothelial cells, which exist in the tumor microenvironment. To test this, they developed a system to grow 3D spheroids of mammary tumor and endothelial cells in hanging drops of cell culture medium in vitro.

Upreti and her team found that the presence of endothelial cells in 3D co-cultures sensitized the tumor cells to chemotherapy while protecting them from ionizing radiation. When implanted in nude mice, the tumor-endothelial spheroids induced more rapid neovascularization, faster tumor growth rate, and greater metastasis than tumor cell-only spheroids. Molecular analysis also revealed pronounced up-regulation of several proangiogenic factors in the tumor tissue derived from the co-culture spheroids.

What Upreti et al. have demonstrated is a new preclinical in vitro model system that allows researchers to comprehensively evaluate cancer therapeutics against an environment similar to occult cancer or micro-metastases to generate more predictive preclinical data. Researchers can easily create the same novel spheroid co-culture system using 3D Biomatrix’s Perfecta3D™ Hanging Drop Plates, which utilizes gravity to form multicellular scaffold-free spheroids whose size and composition can be easily and precisely controlled. Are you ready to be a tumor architect? Create your own co-culture tumor spheroids now!

Source/Image adapted from:
Tumor-Endothelial Cell Three-dimensional Spheroids: New Aspects to Enhance Radiation and Drug Therapeutics http://www.ncbi.nlm.nih.gov/pubmed/22191001