Prostate Tumor Cells

Prostate tumor cells usually arise from the prostatic epithelium, specifically from the cells lining the prostate ducts. These cells can undergo malignant transformation due to a variety of factors, including genetic mutations, hormonal influences, and environmental exposures. Some prostate cancers remain localized to the gland and may not cause significant harm, while others can invade nearby tissues and spread to other parts of the body, such as the bones and lymph nodes, a process known as metastasis.

Characteristics of Prostate Tumor Cells

• Cellular architecture and morphology. Prostate tumor cells exhibit distinct morphological features when compared to normal prostate cells. These tumor cells often display irregular shapes, increased nuclear-to-cytoplasmic ratios, and heterogeneous chromatin patterns. Such features are commonly assessed in histopathological examinations, leading to classification according to the Gleason grading system, which aids in predicting clinical outcomes.
• Genetic alterations. Prostate tumor cells frequently harbor key genetic mutations that contribute to tumorigenesis. Notable among these are alterations in the TP53 and PTEN tumor suppressor genes, which disrupt critical cellular regulatory pathways. Additionally, mutations in the AR gene, responsible for androgen receptor function, are linked to advanced disease and treatment resistance.

Research and Experimental Models

Prostate tumor cells are instrumental in preclinical research, providing insights into tumor biology and treatment efficacy. Utilizing cell lines and patient-derived xenografts allows researchers to study the cellular response to various therapeutics in a controlled environment. Such models are essential for expanding the understanding of the tumor microenvironment and the cellular interactions that drive prostate cancer progression.

Therapeutic Targeting

Prostate tumor cells provide a valuable model for exploring targeted therapeutic approaches. Recently, the development of next-generation inhibitors, such as PARP inhibitors for BRCA-mutated tumors, has gained traction. These therapeutics aim to exploit specific vulnerabilities of prostate tumor cells, thereby improving patient outcomes. Furthermore, immunotherapeutic strategies, including prostate-specific antigen (PSA) vaccines, aim to harness the patient's immune system to target and eliminate tumor cells effectively.

rADAM9D Inhibits the Invasion and Migration of DU145 Prostate Tumor Cells

The ADAM (A Disintegrin And Metalloproteinase) family of proteins comprises a group of multifunctional proteins that play important roles in many biological processes, such as cell fusion, cell adhesion, proteolysis, and in some diseases as well, including cancer. rADAM9D was tested for its ability to inhibit DU145 cell invasion and migration. rADAM9D, at concentrations ranging from 100 to 1000 nM, was able to significantly inhibit DU145 cell invasion (Fig. 1). In a wound healing migration assay, rADAM9D significantly inhibited DU145 cell migration at 100, 500, 1000, and 2000nM (Fig. 2A and B). The effects were more striking after 24 hours of wound repopulation.

Fig. 1 rADAM9D inhibits the invasion of DU145 cells through matrigel. (Martin AC, et al, 2015)

Fig. 2 rADAM9D inhibits the migration of DU145 cells in a wound healing assay. (A) Cells were incubated with ADAM9D (100, 500, 1000, and 2000 nM) for 24 h and 48 h. Only pictures from rADAMD9 500 and 2000 nM are represented. (B) The closure area of migrating cells was measured using ImageJ software, and it was calculated the percentage of wound closure, comparing time zero and 24 hours. Results are expressed as percent of wound closure relative to control (untreated) cells. (Martin AC, et al, 2015)

Ad Efficiently Transduce Human and Mouse Prostate Cancer Cells in Vitro

Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adenovirus (Ad) is the most widely used gene therapy vector. To evaluate the transduction efficiency of Ad in prostate cancer cells in vitro, PC3 and TRAMP-C2 cells, a human and mouse prostate cancer cell line, respectively, were infected with indicated MOI of EGFP-expressing Ad. One day post-infection, the transduction efficiency of Ad was quantitatively profiled by measuring the overall EGFP fluorescence intensity (Fig. 3A, B) and the percentage of EGFP-positive cells (Fig. 3C), respectively. The data showed that Ad transduced TRAMP-C2 cells consistently better than PC3 cells with MOI ranging from 1 to 105 (Fig. 3B, C). Taken together, Ad could efficiently transduce human and mouse prostate cancer cells in vitro in a dose-dependent manner.

Fig. 3 (A) Representative microscopic images showing EGFP fluorescence signal of PC3 and TRAMP-C2 cells infected with indicated MOI of EGFP-expressing Ad vectors. (B) Quantification of EGFP intensity presented in arbitrary unit (a.u.). (C) Percentage of EGFP-positive cells analyzed by flow cytometry. (Ai J, et al., 2017)