Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening.
The lack of effective therapies for bone metastatic prostate cancer (PCa) underscores the need for accurate models of the disease to enable the discovery of new therapeutic targets and to test drug sensitivities of individual tumors. To this end, the patient-derived xenograft (PDX) PCa model using immunocompromised mice was established to model the disease with greater fidelity than is possible with currently employed cell lines grown on tissue culture plastic. However, poorly adherent PDX tumor cells exhibit low viability in standard culture, making it difficult to manipulate these cells for subsequent controlled mechanistic studies. To overcome this challenge, we encapsulated PDX tumor cells within a three-dimensional hyaluronan-based hydrogel and demonstrated that the hydrogel maintains PDX cell viability with continued native androgen receptor expression. Furthermore, a differential sensitivity to docetaxel, a chemotherapeutic drug, was observed as compared to a traditional PCa cell line. These findings underscore the potential impact of this novel 3D PDX PCa model as a diagnostic platform for rapid drug evaluation and ultimately push personalized medicine toward clinical reality.
Departments of Biochemistry and Cell Biology and ‡Bioengineering, Rice University , Houston, Texas 77005, United States.
Eliza L S
EL
Fong
Mariane
M
Martinez
Jun
J
Yang
Antonios G
AG
Mikos
Nora M
NM
Navone
Daniel A
DA
Harrington
Mary C
MC
Farach-Carson
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C410798:AR protein, human; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid