| Nakagawa [40] |
Metastatic colon cancer |
Fibroblasts isolated from 3patients with liver metastasis |
Lack of epithelium specific markers cytokeratin-19 and -20. Positive for vimentin (RT-PCR) and α-SMA (immunofluorescence) |
Increased HCT116 proliferation in vivo
|
Not assessed |
| Nagasaki [41] |
Colon cancer |
Fibroblasts isolated from 64 year old patient |
Lack of cytokeratin, positive for CD90 and vimentin (immunostaining) α-SMA (immunofluorescence) |
Blocking stromal IL-6 decreased tumour growth and angiogenesis in mouse xenograft model |
Not assessed |
| Zhang [42] |
Epithelial Ovarian Carcinoma (EOC) |
Fibroblasts isolated from 61 patients with EOC |
Negative for cytokeratin-8, positive for FAP and vimentin (immunohistochemistry) |
Increased α-SMA staining in advanced disease and in cases with lymph node and omentum metastasis. Positive correlation between α-SMA and lymphatic and microvessel densities In vitro fibroblasts promoted invasion and migration of ovarian cancer |
Not assessed |
| Olumi [44] |
Prostate cancer |
CAFs from 3 prostate cancer patients |
Negative for cytokeratin and positive for α-SMA and vimentin (immunofluorescence) |
CAFs promoted tumour progression when grafted as tissue recombinants into nude mice. Tissue recombinants + CAFs appeared metastatic, recombinants + normal fibroblasts appeared benign |
Not assessed |
| Direkze [33] |
Pancreatic insulinoma |
Fibroblasts isolated from mouse bone marrow |
α-SMA for myofibroblasts vimentin for fibroblasts (immunostaining) |
RIPTag mice administered GFP+ bone marrow via tail vain following whole body irradiation. In pancreatic tumours that developed, 25% of myofibroblats found to be bone marrow derived |
Not assessed |
| Mishra [29] |
Breast Cancer |
In vitro expansion of human bone marrow MSCs. |
α-SMA, vimentin, FSA (immunofluorescence) |
Tumour-conditioned MSCs co-cultured with tumour cell line increased tumour cell growth and proliferation |
Not assessed |
| Spaeth [31] |
Ovarian cancer |
Human bone marrow MSCs |
FSP, FAP, tenascin-c, thrombospondin-1, stromelysin-1, α-SMA, desmin, VEGF (immunohistochemistry) |
Co-injection of MSCs with tumour cells resulted in significantly larger tumours |
Not assessed |
| Erez [34] |
Squamous skin carcinoma |
CAFs isolated from mouse dysplastic skin |
PDGFR- α (flow cytometry) |
Tumours co-injected with CAFs demonstrated enhanced growth and vascularisation |
Co-injection of CAFs resulted in increased recruitment of macrophages which supported increased tumour vascularisation |
| Shainagawa [46] |
Colon cancer |
Human bone marrow MSCs expanded in vitro
|
α-SMA, PDGFR-β, desmin, FSP, FAP (Immunofluorescence) |
Tail vein injection of MSCs into tumour bearing mice. MSCs detected in primary tumour site and liver metastasis. Co-injection of MSCs and tumour cells resulted in enhanced tumour growth, increased PCNA-LI, increased MVA and decreased AI |
Not assessed |
| Koliaraki [37] |
Colon cancer |
Intestinal tissue |
CD45, Ter119, CD31 E-cadherin negative, CD29, CD44, CD104- α positive (Flow cytometry). α-SMA, vimentin, collagen IV (immunohistochemistry) Vimentin, collagen IV (flow cytometry) |
Deletion of Ikkβ in intestinal mesenchymal cells protected against inflammation associated carcinogenesis |
Ikkβ in intestinal mesenchymal cells regulated immune cell infiltrate and cytokine production |
| Pallangyo [38] |
Colon cancer |
Intestinal tissue |
PDGFRα, CD29, CD44 positive, PDGFRβ CD45, Ter119, CD31 EpCAM negative (flow cytometry) Vimentin, FSP, α-SMA (immunofluorescence) |
Lack of Ikkβ in intestinal fibroblasts increases tumour size |
Not assessed |
| Kraman [51] |
Lewis lung carcinoma and pancreatic ductal adenocarcinoma |
Mouse tumour tissue |
FAP, α-SMA, Col I (Immunostaining) |
|
LLC – depletion of FAP+ cells induced necrosis of tumour cells. PDA – depletion of FAP+ cells allowed immunogenic control of tumour growth |
| Feig [52] |
Pancreatic ductal adenocarcinoma |
Mouse tumour tissue |
FAP, α-SMA (Immunostaining) PDGFR- α positive, CD45 negative (Flow cytometry) |
|
Inhibiting CXCR4, a receptor for FAP+ stromal cell CXCL12 promoted T cell accumulation and synergised with checkpoint antagonists resulting in tumour regression |
| Calon [49] |
Colon cancer |
Human colon adenoma and carcinoma tissue |
FAP |
Pharmacological inhibition of stromal cell TGF-β signalling blocked initiation of metastasis |
Not assessed |
