Lifeline® Cells: Better Normal Controls for Therapeutic Development
Identifying the best cells to use as controls is critical. In particular, finding a “normal”, non-cancer control cell to test anti-cancer therapies is a challenge our customers often face. Lifeline® has the tools to help – read on to learn more.
The phrase “normal cells” can sometimes be misleading. In fact, “normal” immortalized cell lines are not as normal as they might seem. To generate cell lines for research that are able to indefinitely grow in culture requires genetic manipulation of certain cell cycle genes. This allows cells to avoid onset of senescence, which occurs naturally when non-transformed cells are grown on plastic. Importantly, these manipulations are typically induced using viral delivery of DNA, which permanently alters the identity of the cell, and may also affect its behavior.
The ideal normal control cell from the same tissue of interest would not be manipulated in any way, yet able to grow in culture for a reliable number of passages. Luckily, Lifeline® has what you need. Lifeline® offers an extensive catalog of normal cells from sixteen different tissue types, including:
Our customers use Lifeline® cells often in their research to demonstrate that a cancer therapy is specific for cancer cells and does not affect normal cells. This is a critical characteristic that is a hallmark of any cancer therapy, and Lifeline® cells serve as excellent control cells for these experiments. Below are just a few studies from our customers demonstrating the utility of Lifeline® cells for testing the efficacy of cancer-specific agents.
STAT3 inhibition in prostate and pancreatic cancer lines by STAT3 binding sequence oligonucleotides: differential activity between 5′ and 3′ ends. Lewis et al. developed anti-STAT3 oligonucleotides to inhibit STAT3 function in cancer. They found that while the oligonucleotides were active in prostate and pancreatic cancer cells, Lifeline® normal human dermal fibroblasts were unaffected.
USP8 is a novel target for overcoming gefitinib resistance in lung cancer. Byun et al. demonstrated that USP8 is a therapeutic target in lung cancer that is resistant to anti-epidermal growth factor receptor therapy. They abrogated USP8 function by either USP8 knockdown or treatment with a USP8 inhibitor in lung cancer cells, which resulted in cancer cell apoptosis. Importantly, they illustrated that Lifeline® human bronchial/tracheal epithelial cells were unaffected by loss of USP8 function.
CLT1 targets bladder cancer through integrin α5β1 and CLIC3. Knowles and colleagues investigated the effects of treating cancer cells with CLT1, an anti-angiogenic peptide. They found that CLT1 treatment selectively killed bladder, kidney, lung, breast, and prostate cancer cells, while having no effect on Lifeline® human bladder epithelial cells.
Blocking the formation of radiation-induced breast cancer stem cells. Wang et al. tested the efficacy of combined radiation and disulfiram therapy in breast cancer. They demonstrated that this combination therapy decreased tumor growth and metastasis, and decreased tumor stemness. Importantly, this therapeutic approach was not toxic toward Lifeline® human mammary epithelial cells.
Inhibition of PI3K/AKT/mTOR axis disrupts oxidative stress-mediated survival of melanoma cells. Cancer cells acquire the ability to proliferate in conditions of low oxygen, or oxidative stress. Hambright et al. illustrated that NexrutineR decreased the oxidative stress response in melanoma cells, resulting in decreased tumor-promoting activity. Using Lifeline® human epidermal neonatal melanocytes, they showed that NexrutineR had no effect on normal, non-transformed cells.
Englerin A selectively induces necrosis in human renal cancer cells. Sulzmaier and colleagues investigated the utility of using Englerin A to treat renal cancer. They showed that Englerin A was cytotoxic to renal cancer cells, but had no effect on Lifeline® renal proximal tubule epithelial cells.
Together, these and other studies demonstrate the great utility of Lifeline® cells to accurately represent a normal tissue control for the investigation of cancer therapeutics. Lifeline® cells have many other applications, which are highlighted on our blog. Please visit the Lifeline Cell Technology main blog page to read more about how Lifeline® cells can be useful for your research applications.
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