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Epithelial Cells — Guardians of the Internal Environment — and the Latest Cancer Studies

September 4, 2016 / by Lifeline® Cell Technology

Epithelial cells line multiple organs throughout the body, including the gastrointestinal tract, bladder, uterus, and airway. Epithelial cells are arranged in sheets, each cell closely connected to its neighbors through attachments called tight junctions. Epithelial cells often sit at the interface between the outside environment and the internal milieu. Here, tightly-packed sheets of epithelial cells communicate with the external environment, giving and receiving signals, and allowing transport of certain molecules through the epithelial layer into the bloodstream. Epithelial cells are also the cell of origin for many solid tumors, including colorectal carcinoma, lung carcinoma, renal cell carcinoma, prostate carcinoma, and others.

Recent Studies Featuring Lifeline® Epithelial Cells

Tumor necrosis-related apoptosis-inducing ligand (TRAIL) is a cancer therapy that works by inducing cancer cell apoptosis, while sparing normal cells. However, TRAIL treatment can be complicated as resistance often develops. To address this, there has been an effort to discover compounds that sensitize cancers to TRAIL therapy. In a 2015 study, Henrich et al. explored the TRAIL-sensitizing effects of withanolide E, a compound purified from P. peruviana, a plant found in South America. The group found that withanolide E had a significant effect on renal cancer cell growth when combined with TRAIL treatment. The researchers also tested the effects of combined TRAIL and withanolide E treatment on Lifeline® human renal epithelial cells and found that the treatment had minimal effects on cell growth, suggesting that this therapeutic approach largely affects cancer cells, while leaving normal cells relatively unaffected. The researchers investigated the mechanism of withanolide E-induced TRAIL sensitization and found that renal carcinoma cells underwent apoptosis following decreased cellular cFLIP levels that may be due to impaired HSP90 activity. HSP90 is a chaperone protein that is targeted by withanolide E; cFLIP is a HSP90 client, and therefore, impaired HSP90 activity may lead to aggregation and/or misfolding of cFLIP. Finally, activation of the TRAIL receptor in a xenograft mouse model of renal carcinoma cells, combined with withanolide E treatment significantly decreased tumor size, and in some cases, eliminated tumors completely. Together, these results suggest that withanolide E is a promising therapeutic agent that could be used in conjunction with TRAIL to promote TRAIL sensitization in cancer therapy.

 

Glycosylation is the process by which carbohydrate moieties are added to cellular molecules. The function, localization, and expression of proteins are often mediated by glycosylation, and dysregulated glycosylation has been implicated in transformation. In a 2015 study, Yang et al. defined the glycosylation patterns of CUB-domain-containing protein 1 (CDCP1), a protein that is overexpressed in metastatic prostate cancer. They found that there were two main cellular forms of CDCP1, a high molecular weight form and a low molecular weight form. They observed that the high molecular weight, full-length form of CDCP1 was found in the majority of prostate-derived cells they analyzed. Interestingly, in syngenic prostate cancer cell lines for which a metastatic line was available, the full-length form was expressed more highly in the metastatic line compared to the non-metastatic line. The researchers used Lifeline® human prostate epithelial cells as normal control cells and found that these cells expressed only the full-length form of CDCP1. They also found that full-length CDCP1 was glycosylated, glycosylation was required for its cell surface localization, and inhibition of glycosylation promoted the expression of the lower molecular weight form of CDCP1, a proteolytic product. Additionally, the researchers found that the structure of the CDCP1-associated glycan group differed between metastatic and non-metastatic cell pairs, suggesting that prostate cancer cell metastasis is associated with a certain form of CDCP1 glycosylation. CDCP1 was also present in extracellular vesicles as a full-length protein that maintained the glycosylation status of the parent cells. Finally, the researchers were able to detect CDCP1 in the urine of prostate cancer patients and observed that CDCP1 was present at higher levels in patients with high-risk disease. Together, the results of this study suggest that CDCP1 glycosylation is important for proper localization of full length CDCP1 and altered glycosylation is associated with metastatic prostate cancer cell lines. CDCP1 is also detectable in patient urine samples and may indicate a higher risk for prostate cancer.

 

Hypoxia, or conditions of low oxygen, occurs in various disease contexts, including inflammation and cancer. In hypoxic conditions, cells have ways of compensating for low oxygen by lowering metabolic activity and slowing growth. Common methods of measuring cellular hypoxia are not suitable for diagnostics, and therefore, Silina et al. set out to develop a mass spectrometry-based method to measure hypoxia in a way that could be useful for diagnostics. Using Lifeline® primary lobar bronchial epithelial cells in all of their experiments, the researchers used hydrophilic interaction chromatography-electroscopy ionization-mass spectrometry (HILIC-ESI-MS) to identify a compound, p-coumaric acid, that serves as a marker of cellular hypoxia. p-Coumaric acid is involved in cellular respiration as a precursor of co-enzyme Q10, an important participant of the electron transport chain. The researchers found that in hypoxic conditions, the level of p-coumaric acid increased and could be reliably detected by HILIC-ESI-MS. They conclude that this detection method is very sensitive and can be used to measure the expression of p-coumaric acid as a readout for cellular hypoxia for diagnostic purposes.

Lifeline® provides human epithelial cells and corresponding optimized growth medium from multiple organ sites, including:

Let us know how you are using Lifeline® cells for your research and your study could be featured here on our blog!

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