The role of cancer-associated fibroblasts in cancer (Source: Roy, Aniruddha & Li, Shyh-Dar. (2016). Modifying the tumour microenvironment using nanoparticle therapeutics. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology. 8. 10)
According to GLOBOCAN 2018 data published in CA: A Cancer Journal for Clinicians, gastric or stomach cancer leads not only in being the most common but also deadly. It ranks third in causing deaths across the world with lung cancer and colorectal cancer at the top positions. In terms of prevalence, it occupies the 7th position and is globally the 5th most commonly diagnosed cancer (5.7% of the new diagnosis of cancer is gastric cancer). One out of twelve deaths due to cancer is due to gastric cancer.
According to In-hye Ham and team in the Hindawi Journal of Oncology (2019), the overall survival rate of gastric cancer patients despite standard treatment is 20%–40% with the time shortening to lesser than 10 months for stage IV patients. Early research in Cancer Research by Kaplan reported the role of the microenvironment of cancerous cells. It is this tumour environment that is implicated in the resistance to treatment approaches. The environment is made up of the cancer cells, extracellular matrix (ECM), fibroblasts, immune cells, cancer stem cells, pericytes along with cancer stem cells.
The development of cancer sees the vital involvement of cancer-associated fibroblasts (CAFs). These cells secrete growth factors and cytokines to control the metabolism of cancer cells, promote cell migration and increase the resistance to molecules used for treatment (Hindawi Journal of Oncology, 2019). The use of in vitro tumour models using cell cultures has shown these effects caused by CAFs.
The involvement of specific gastric CAFs (GCAFs) on cancer and the identification of unique biomarkers of these cells are yet to be reported in detail. To assist such studies, Ma and team reported primary cultures of CAFs from gastric cancer patients in Cancer Cell International in 2018.
Post-washing, 1-mm3 pieces of the tissue were digested using trypsin followed by culture in DMEM with 20% FBS and antibiotics. The cultures established revealed interesting observations. The expression of a GCAF cell marker called fibroblast activation protein (FAP) was associated with poor survival of patients to hence, serve as a prognosis marker.
The isolated cells showed the expected morphology and the presence of markers such as FAP, vimentin and desmin. Subsequent tests using cells isolated from the primary culture showed that GCAFs not only increased the migratory abilities of gastric cancer cells but also their ability to invade. Another interesting finding was resistance induced in stomach cancer cell lines to the commonly used anti-cancer drug called 5-fluorouracil (5-FU). The medium used to culture the GCAFs called conditioned medium caused this resistance with the possible role of molecules that target the mitochondria.
Thus, primary cultures allow for gaining new insights into the pathways associated with deadly diseases like cancer. The functioning of the tumour microenvironment can be assessed more in detail to target molecules or cells such as GCAFs discussed here to get cues of treating the dreaded “C” (cancer).
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
CA: A Cancer Journal for Clinicians. 2018 Nov; 68(6):394-424.
In-Hye Ham, Dagyeong Lee, and Hoon Hur. Role of Cancer-Associated Fibroblast in Gastric Cancer Progression and Resistance to Treatments. Hindawi Journal of Oncology 2019. Article ID 6270784: 11 pages.
Kaplan RN, Rafii S, Lyden D. Preparing the “soil”: the premetastatic niche. Cancer Research. 2006;66(23):11089–93.
Ma Y, Zhu J, Chen S , et al. Activated gastric cancer-associated fibroblasts contribute to the malignant phenotype and 5-FU resistance via paracrine action in gastric cancer. Cancer Cell International. 2018; 18, 104.