Fibroblasts: Roles in Homeostasis, Wound Healing, and Cancer
Fibroblasts are one of the most common types of stromal cells in the body and are responsible for generating extracellular matrix (ECM) components that support the tissue in which they exist. There is tremendous crosstalk between fibroblasts in the stroma and the epithelium or endothelium in a given organ, which is important in maintenance of normal tissue function. Fibroblasts not only play a role in tissue homeostasis, but also are critical players in wound healing. Additionally, fibroblasts play a significant role in cancer. When fibroblasts become activated, they begin to secrete large amounts of ECM, which when regulated, aids in wound healing. However, in cancer, activated fibroblasts are often dysregulated, and continue to produce ECM, leading to enhanced tumor stroma. These cancer-associated fibroblasts (CAFs) can therefore alter the tumor microenvironment to enhance tumor progression.
Lifeline® fibroblasts featured in recent research
Measuring the health and viability of cells in culture is critical for evaluating the efficacy of therapeutics. In a 2015 study, Caporizzo et al. investigated the feasibility of using viscoelasticity as a readout of cell viability. The rationale behind these experiments is that cells often become more rigid as they experience toxicity; therefore, increased stiffness should indicate decreased viability. To do this, the authors use atomic force microscopy, followed by a variable indentation-rate analysis, or VIVA, to determine cell relaxation time and stiffness. They first compared the properties of Lifeline® human adult dermal fibroblasts, Lifeline® human umbilical vein endothelial cells (HUVECs), and THP-1 cells, a leukemia cell line. They found that of the three cell types, fibroblasts were the stiffest, followed by HUVECs and THP-1 cells, which were the softest. Additionally, HUVECs had the longest relaxation time, with fibroblasts and THP-1 cells having similar, shorter relaxation times. These characteristics are consistent with the migratory properties of fibroblasts and THP-1 cells.
The remainder of their experiments were focused on the response of THP-1 cells to treatment with rhodamine or silver nanoparticles, delivered using a dextran-lysozyme carrier. The authors found that silver nanoparticles decreased cell viability to 62%, while rhodamine had a less significant effect, decreasing viability to 90%. Additionally, rhodamine and silver nanoparticles increased the stiffness of THP-1 cells, consistent with their effects on viability. Together, the results of this study suggest that viscoelasticity reflects cell viability and can be used to measure the effects of cytotoxic therapeutics in vitro.
Angiomodulin (AGM) is a glycoprotein often expressed in tumor vasculature and implicated in cancer. In a 2012 study in Cancer Science, Komiya and colleagues described the expression of AGM in tumor tissues and investigated the mechanism by which AGM might play a role in tumor progression. The researchers found that in colon, lung, and uterine cancer samples, AGM was largely expressed in stromal cells, including fibroblasts, as well as in the tumor vasculature. To further elucidate the role of AGM in tumorigenesis, the researchers treated Lifeline® human neonatal dermal fibroblasts with transforming growth factor-b (TGF-b), a fibroblast-activating growth factor that stimulates production of a-smooth muscle actin (a-SMA) and ECM components. They found that TGF-b treatment induced fibroblast production of AGM, as well as a-SMA and fibronectin, an ECM protein. Additionally, they found that AGM treatment of fibroblasts had a similar induction effect. Finally, they found that TGF-b and AGM had opposite effects on fibroblast cell growth: TGF-b decreased cell growth, while AGM increased cell growth. In contrast to their opposing effects on cell growth, both TGF-b and AGM slightly increased fibroblast migration. Together, the results of this study demonstrate that AGM activates fibroblasts in cooperation with TGF-b signaling, leading to increased stromal activity and tumor progression.
Lifeline® fibroblasts for your research needs
Lifeline® offers fibroblasts from multiple organ sites, including:
Lifeline® fibroblasts are optimized for growth in FibroLife® S2 or FibroLife® Serum Free fibroblast medium for at least 15 population doublings. Additionally, Lifeline® fibroblasts can be used as feeder cells for embryonic stem cell (ES cell) cultures. Lifeline® human dermal fibroblasts have also been validated for generation of induced pluripotent stem cells (iPSCs).
It is a new year and we are always looking to highlight new research here on our blog. Let us know how you are using Lifeline® cells to answer your scientific questions and we will feature your work here!