In Vitro Three-Dimensional Culture System Enhances Prostate Cancer Cell Growth

A team of cancer researchers developed a three-dimensional in vitro culture system for growing prostate cancer cells in an environment that closely mimics the in vivo tumor microenvironment.

The physical and mechanical properties of the tumor microenvironment are crucial for the growth, differentiation, and migration of cancer cells. However, such a microenvironment is not reproduced in vitro due to the geometric constraints of the classic two-dimensional cell culture systems used in many cancer studies. Prostate cancer research, in particular, suffers from the lack of suitable in vitro models.

To correct this deficiency, investigators at the Karlsruhe Institute of Technology (Eggenstein-Leopoldshafen, Germany) generated a three-dimensional in vitro growth system based on a superporous scaffold prepared by cryogelation of poly(ethylene glycol) diacrylate. The resulting structure was a defined elastic matrix for prostate tumor growth with mechanical properties that were very similar to those of natural cell tissue.

The investigators reported in the May 30, 2016, online edition of the journal Small that lymph node carcinoma of the prostate (LNCaP) cells showed a linear growth over 21 days as multicellular tumor spheroids in such a scaffold with points of attachments to the walls of the scaffold. These LNCaP cells responded to the growth promoting effects of androgens and demonstrated a characteristic cytoplasmic-nuclear translocation of the androgen receptor and androgen-dependent gene expression.

Compared to two-dimensional cell culture, the expression or androgen response of prostate cancer specific genes was greatly enhanced in the LNCaP cells grown in the three-dimensional system.

"The paper covers the implementation of the model and shows that it is a long-term stable tissue-like three-dimensional cell culture system, with the help of which hormone-independent prostate-specific gene expression could not only be achieved, but even be reinforced compared to conventional two-dimensional models," said contributing author Dr. Friederike J. Gruhl, a researcher in the Institute of Microstructure Technology at the Karlsruhe Institute of Technology. "This was shown by the cultivation of androgen-sensitive prostate cancer cells (LNCaP). In future, it may be possible to cultivate both healthy cells of the prostate tissue and cancer cells in the three-dimensional cryogel model. This opens up new opportunities for preclinical research and for using it in the clinical development of anti-prostate cancer drugs."

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Karlsruhe Institute of Technology