PC3 (PC-3) is a human prostate cancer cell line used in prostate cancer research and drug development. [1] PC3 cells are useful in investigating biochemical changes in advanced prostate cancer cells and in assessing their response to chemotherapeutic agents. PC3 cells are also used to study viral infection in mammalian cells that exhibit an immune response. [2]
The PC3 cell line was established in 1979 from bone metastasis of grade IV of prostate cancer in a 62-year-old Caucasian male. [3] These cells do not respond to androgens, glucocorticoids or fibroblast growth factors, [4] but results suggest that the cells are influenced by epidermal growth factors. [5] PC3 cells can be used to create subcutaneous tumor xenografts in mice to investigate the tumor environment and therapeutic drug functionality. [6]
PC3 cells have high metastatic potential compared to other pancreatic cells of DU145 cells, which have a moderate metastatic potential, and to LNCaP cells, which have low metastatic potential.[ citation needed ] Comparisons of the protein expression of PC3, LNCaP, and other cells have shown that PC3 is characteristic of small cell neuroendocrine carcinoma. [4]
PC3 cells have low testosterone-5-alpha reductase and acidic phosphatase activity, and do not express PSA (prostate-specific antigen). Furthermore, karyotypic analysis has shown that PC3 are near-triploid, having 62 chromosomes. Q-band analysis showed no Y chromosome. From a morphological point of view, electron microscopy revealed that PC3 cells show characteristics of a poorly-differentiated adenocarcinoma. They have features common to neoplastic cells of epithelial origins, such as numerous microvilli, junctional complexes, abnormal nuclei and nucleoli, abnormal mitochondria, annulate lamellae, and lipoidal bodies.[ citation needed ]
There are a variety of Different PC3 cell lines derived from the original PC3 cell line. The most common include PC3-PR Cells, PC-3M Cells, PC3-EGFP Cells, PC3-Dox Cells, PC3-LacZ Cells, PC3-AR Cells. Each of these have different morphological and physiological properties but they all originate from the original PC3 cell derived from the 62-year old caucasian male. [3]
C3-PR cells are Paclitaxel-Resistant cells that, unlike PC3 cells, are resistant with Paclitaxel (PTX). In these cells PTX is unable to stimulate p21 and acetylated α-tubulin expression of PC3-PR cells. Though Cabazitaxel and HDAC inhibitors were able to induce p21 and α-tubulin, these equally suppress PC3-PR cells. Due to the suppression ability of Cabazitaxel and HDAC, these drugs are able to replace the common chemotherapy drug in PC3-PR cells. [7] These cells allow researchers to develop strategies in order to treat prostate cancer that is resistant to traditional chemotherapy drugs.
PC-3M Cells (Metastatic)
PC-3-M cells are a highly metastatic form of PC3 cells. They metastasize in a much more prolific fashion than regular PC3 cells. These cells are used in research to study the potential treatments of PC’s that are highly metastatic. PC3-M is used in research from in-vitro to in-vivo model animals for cancer research. [8] This cell line is able to research the most dangerous, advanced forms of pancreatic cancer, as the high metastasis potential will allow these cells to spread throughout the body in a rapid fashion.
PC3-EGFP Cells (Enhanced Green Fluorescent Protein)
PC3-EGFP are PC3 cells that have been modified in order to express green fluorescent proteins at a higher rate. This is visible when EGFP expression levels are analyzed. [9] This allows for live tracking of PC3 cells as well as real time imaging. This can be especially useful when studying the proliferation as well as the drug response in PC3 cells.
PC3-Dox Cells
PC3-Dox cells are modified to be resistant to Doxorubicin. This cell line is used to study multidrug resistance (MDR) in PC3. Specifically miR-21 research is based on this lineage of cells in order to determine if it is possible to reverse (MDR) through the employment of this drug. Additionally these cells look at if it is possible to resensitize PC3 cells to Doxorubicin. [10]
PC3-Ras Cells PC3-Ras cells are modified in order to express the oncogene ras. Ras is involved in the activation of downstream effectors that play a role in DNA transcription. This modification allows researchers to study the role of Ras signaling in prostate cancer. This is very important to studying the processes of tumor progression, metastasis, and drug resistance in pancreatic cancer cells, as it is tied to mitosis. [11]
Prostate cancer (PC) is the most common form of non-cutaneous malignant cancer in males, and is the second leading cause of cancer deaths in males. [12] PC3 cells have been utilized to research aggressive and castration-resistant forms of prostate cancer. The androgen-independence of these cells during cell division makes them invaluable for studying the molecular mechanisms embedded in studying advanced prostate cancer. [13] PC3 cells have been involved in research regarding the prevention and treatment of prostate cancer. PC3 cells have been used in research surrounding Methylene Blue Photodynamic Laser Therapy (MB-PDT) and Sulforaphane (SFN). Research published in 2023 utilizing PC3 cells illustrated that MB-PDT treatment decreased the antioxidant potential and increased lipid peroxidation, decreasing the viability and metastatic capacity of PC3 cells. The results from this study further support other research that MB-PDT can be used in conjunction with traditional therapies to treat aggressive versions of prostate cancers. [14] SFN treatments have been used to treat prostate cancer as well as many other tumors. SFN is a plant-derived chemical present in many plants, especially broccoli and broccoli sprouts; though there are concerns about the bioavailability of SFN supplements. [15] Nevertheless, many prostate cancer patients have turned to SFN to prevent growth of PCs resistant to many of the traditional forms of treatment. Experimentation in 2020 linked SFN to a decrease in prostate cancer proliferation and growth, using PC3 cells alongside DU145. These studies found that using treatments as low as 1 µM of SFN decreased PC3 cell count by 50% in-vitro. [16]
Prostate cancer is the uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of prostate tissue is usually detected through screening tests, typically blood tests that check for prostate-specific antigen (PSA) levels. Those with high levels of PSA in their blood are at increased risk for developing prostate cancer. Diagnosis requires a biopsy of the prostate. If cancer is present, the pathologist assigns a Gleason score, and a higher score represents a more dangerous tumor. Medical imaging is performed to look for cancer that has spread outside the prostate. Based on the Gleason score, PSA levels, and imaging results, a cancer case is assigned a stage 1 to 4. A higher stage signifies a more advanced, more dangerous disease.
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.
Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with paracrine signaling, intracrine signaling, or classical endocrine signaling.
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma is more aggressive, with a shorter doubling time, higher growth fraction, and earlier development of metastases.
LNCaP cells are a cell line of human cells commonly used in the field of oncology. LNCaP cells are androgen-sensitive human prostate adenocarcinoma cells derived from the left supraclavicular lymph node metastasis from a 50-year-old caucasian male in 1977. They are adherent epithelial cells growing in aggregates and as single cells.
Cancer stem cells (CSCs) are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with metastatic disease.
The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression.
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
DU145 (DU-145) is a human prostate cancer cell line. DU145, PC3, and LNCaP are considered to be the standard prostate cancer cell lines used in therapeutic research.
G-protein coupled receptor 31 also known as 12-(S)-HETE receptor is a protein that in humans is encoded by the GPR31 gene. The human gene is located on chromosome 6q27 and encodes a G-protein coupled receptor protein composed of 319 amino acids.
Leukotriene B4 receptor 2, also known as BLT2, BLT2 receptor, and BLTR2, is an Integral membrane protein that is encoded by the LTB4R2 gene in humans and the Ltbr2 gene in mice.
RhoC is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC.
A metastasis suppressor is a protein that acts to slow or prevent metastases from spreading in the body of an organism with cancer. Metastasis is one of the most lethal cancer processes. This process is responsible for about ninety percent of human cancer deaths. Proteins that act to slow or prevent metastases are different from those that act to suppress tumor growth. Genes for about a dozen such proteins are known in humans and other animals.
A circulating tumor cell (CTC) is a cancer cell from a primary tumor that has shed into the blood of the circulatory system, or the lymph of the lymphatic system. CTCs are carried around the body to other organs where they may leave the circulation and become the seeds for the subsequent growth of secondary tumors. This is known as metastasis, responsible for most cancer-related deaths.
Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic castration-resistant prostate cancer, and metastatic castration-sensitive prostate cancer (mCSPC). It is taken by mouth.
Cixutumumab (IMC-A12) is a human monoclonal antibody for the treatment of solid tumors.
In medicine, desmoplasia is the growth of fibrous connective tissue. It is also called a desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.
Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that result from primary tumor invasions into bones. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing sarcoma are rare; the most common bone tumor is a metastasis. Bone metastases can be classified as osteolytic, osteoblastic, or both. Unlike hematologic malignancies which originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone. Primary breast cancer patients are particularly vulnerable to develop bone metastases. Bone metastases, especially in a state of advanced disease, can cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.
12-Hydroxyeicosatetraenoic acid (12-HETE) is a derivative of the 20 carbon polyunsaturated fatty acid, arachidonic acid, containing a hydroxyl residue at carbon 12 and a 5Z,8Z,10E,14Z cis–trans configuration (Z=cis, E=trans) in its four double bonds. It was first found as a product of arachidonic acid metabolism made by human and bovine platelets through their 12S-lipoxygenase (i.e. ALOX12) enzyme(s). However, the term 12-HETE is ambiguous in that it has been used to indicate not only the initially detected "S" stereoisomer, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE or 12S-HETE), made by platelets, but also the later detected "R" stereoisomer, 12(R)-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (also termed 12(R)-HETE or 12R-HETE) made by other tissues through their 12R-lipoxygenase enzyme, ALOX12B. The two isomers, either directly or after being further metabolized, have been suggested to be involved in a variety of human physiological and pathological reactions. Unlike hormones which are secreted by cells, travel in the circulation to alter the behavior of distant cells, and thereby act as endocrine signalling agents, these arachidonic acid metabolites act locally as autocrine signalling and/or paracrine signaling agents to regulate the behavior of their cells of origin or of nearby cells, respectively. In these roles, they may amplify or dampen, expand or contract cellular and tissue responses to disturbances.
BxPC-3 (BxPC3) is a human pancreatic cancer cell line used in the study of pancreatic adenocarcinomas and treatments thereof.
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