Tumour-microenvironment interactions: role of tumour stroma and proteins produced by cancer-associated fibroblasts in chemotherapy response
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- Hale, M.D., Hayden, J.D. & Grabsch, H.I. Cell Oncol. (2013) 36: 95. doi:10.1007/s13402-013-0127-7
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Cytotoxic chemotherapy improves survival for some, but not all, cancer patients. Non-responders may experience unnecessary toxicity and cancer progression, thus creating an urgent need for biomarkers that can predict the response to chemotherapy. So far, the search for such biomarkers has primarily been focused on the cancer cells and less on their surrounding stroma. This stroma is known to act as a key regulator of tumour progression and, in addition, has been associated with drug delivery and drug efficacy. Fibroblasts represent the major cell type in cancer-associated stroma and they secrete extracellular matrix proteins as well as growth factors. This Medline-based literature review summarises the results from studies on epithelial cancers and aimed at investigating relationships between the quantity and quality of the intra-tumoral stroma, the cancer-associated fibroblasts, the proteins they produce and the concomitant response to chemotherapy. Biomarkers were selected for review that are known to affect cancer-related characteristics and patient prognosis.
The current literature supports the hypothesis that biomarkers derived from the tumour stroma may be useful to predict response to chemotherapy. This notion appears to be related to the overall quantity and cellularity of the intra-tumoural stroma and the predominant constituents of the extracellular matrix.
Increasing evidence is emerging showing that tumour-stroma interactions may not only affect tumour progression and patient prognosis, but also the response to chemotherapy. The tumour stroma-derived biomarkers that appear to be most appropriate to determine the patient’s response to chemotherapy vary by tumour origin and the availability of pre-treatment tissue. For patients scheduled for adjuvant chemotherapy, the most promising biomarker appears to be the PLAU: SERPINE complex, whereas for patients scheduled for neo-adjuvant chemotherapy the tumour stroma quantity appears to be most relevant.
KeywordsTumour-microenvironment Stroma Fibroblasts Chemotherapy response Prognosis Extracellular matrix
cancer associated fibroblast
cyclophosphamide methotrexate and 5-fluorouracil
connective tissue growth factor
enzyme linked immunosorbent assay
hepatocyte growth factor
protein tyrosine kinase
small cell lung cancer
serine protease inhibitor type-1
secreted protein, acidic, cysteine-rich
tissue inhibitor of metalloproteinase-1
urokinase-type plasminogen activator