Table 1 Identification of CAFs via markers and elucidation of their role in tumor progression
Cancer type | CAFs marker | In vivo model | Findings | Ref. |
|---|---|---|---|---|
BC | Cav-1 | Human breast cancer tamoxifen resistance models: Co-injection of human breast cancer cells (MDA-MB-231) and stromal fibroblasts (wild-type vs. Cav-1-deficient) | Cav-1-deficient stromal fibroblasts release metabolites in a paracrine manner via glycolysis to support angiogenesis and proliferation in breast cancer | [266] |
OSCC | α-SMA | Subcutaneous tumor mouse model: different groups of cells were injected into the abdomen of mice, including HSC3-Ctrl & CAFs-Ctrl, HSC3-Ctrl & CAFs-ITGB2 | ITGB2 regulates the PI3K/AKT/mTOR pathway, enhancing glycolytic activity in CAFs and releasing lactate to promote OSCC proliferation | [58] |
NPC | α-SMA, FAP | Subcutaneous tumor mouse model: NPC cells were injected subcutaneously into mice along with fibroblasts | The NF-κB p65 pathway activates CAFs and promotes aerobic glycolysis and autophagy, thereby increasing cancer cell proliferation and migration | [196] |
PCa | FSP-1 | NG | p62 deficiency in stromal fibroblasts leads to asparagine production through regulating the pyruvate carboxylase-asparagine synthase cascade reaction, which provides the raw material for stromal cell and tumor epithelial cell proliferation | [267] |
CRC | α-SMA | Subcutaneous tumor mouse model: CRC cells were injected subcutaneously into the spleen of nude mice with CAFs or fibroblasts | Reprogramming of lipid metabolism in CAFs enhances colorectal cancer cell migration | [47] |
PCa | Tenascin C, FAP | Tissue recombination mouse models: epithelial cells were mixed with CAFs or stromal cells to prepare cellular recombinants and collagen plugs placed in the anterior prostate and under the renal capsule of C57BL/6 male mice to establish tumor models | CAFs drive glutamine synthesis through oncogenic Ras activity and serve as an energy source to promote neuroendocrine prostate cancer reprogramming | [252] |
BC | α-SMA; FAP | Subcutaneous tumor mouse model (animals were subcutaneously injected with BC cells and different subgroups of CAFs) | Enhanced oxidative ATM-mediated glycolysis in breast cancer-associated fibroblasts promotes tumor invasion via lactate as metabolic coupling | [55] |
PCa | α-SMA | Subcutaneous tumor mouse model (animals were injected subcutaneously with wild-type or MCT1-silenced PCa together with CAFs) | CAFs undergoing Warburg metabolism and mitochondrial oxidative stress can program prostate cancer cells to follow aerobic metabolism, thereby driving tumor cell growth | [60] |
OVCA | NG | Orthotopic OVCA mouse model: subcutaneous injection of tumor cells into mice | High expression of glutaminase in CAFs favors glutamine metabolism and supports proliferation and metastasis of ovarian cancer | [69] |
PDAC | α-SMA | Subcutaneous tumor mouse model: PDAC cells and pancreatic stellate cells were injected into mice | Differentiation of pancreatic stellate cells into CAFs occurs during lipid metabolism, promoting progression of PDAC | [66] |