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See detailIn search of definitions: Cancer-associated fibroblasts and their markers
Nurmik, Martin UL; Ullmann, Pit UL; Rodriguez, Fabien UL et al

in International Journal of Cancer (2019)

The tumor microenvironment has been identified as one of the driving factors of tumor progression and invasion. Inside this microenvironment, cancer-associated fibroblasts (CAFs), a type of perpetually ... [more ▼]

The tumor microenvironment has been identified as one of the driving factors of tumor progression and invasion. Inside this microenvironment, cancer-associated fibroblasts (CAFs), a type of perpetually activated fibroblasts, have been implicated to have a strong tumor-modulating effect and play a key role in areas such as drug resistance. Identification of CAFs has typically been carried based on the expression of various "CAF markers", such as fibroblast activation protein alpha (FAP) and alpha smooth muscle actin (αSMA), which separates them from the larger pool of fibroblasts present in the body. However, as outlined in this Review, the expression of various commonly used fibroblast markers is extremely heterogeneous and varies strongly between different CAF subpopulations. As such, novel selection methods based on cellular function, as well as further characterizing research, are vital for the standardization of CAF identification in order to improve the cross-applicability of different research studies in the field. The aim of this review is to give a thorough overview of the commonly used fibroblast markers in the field and their various strengths and, more importantly, their weaknesses, as well as to highlight potential future avenues for CAF identification and targeting. [less ▲]

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See detailTranscriptional variations in the wider peritumoral tissue environment of pancreatic cancer
Bauer, Andrea S.; Nazarov, Petr V.; Giese, Nathalia A. et al

in International Journal of Cancer (2018), 142(5), 10101021

Transcriptional profiling was performed on 452 RNA preparations isolated from various types of pancreatic tissue from tumour patients and healthy donors, with a particular focus on peritumoral samples ... [more ▼]

Transcriptional profiling was performed on 452 RNA preparations isolated from various types of pancreatic tissue from tumour patients and healthy donors, with a particular focus on peritumoral samples. Pancreatic ductal adenocarcinomas (PDAC) and cystic tumours were most different in these non-tumorous tissues surrounding them, whereas the actual tumours exhibited rather similar transcript patterns. The environment of cystic tumours was transcriptionally nearly identical to normal pancreas tissue. In contrast, the tissue around PDAC behaved a lot like the tumour, indicating some kind of field defect, while showing far less molecular resemblance to both chronic pancreatitis and healthy tissue. This suggests that the major pathogenic difference between cystic and ductal tumours may be due to their cellular environment rather than the few variations between the tumours. Lack of correlation between DNA methylation and transcript levels makes it unlikely that the observed field defect in the peritumoral tissue of PDAC is controlled to a large extent by such epigenetic regulation. Functionally, a strikingly large number of autophagy-related transcripts was changed in both PDAC and its peritumoral tissue, but not in other pancreatic tumours. A transcription signature of 15 autophagy-related genes was established that permits a prognosis of survival with high accuracy and indicates the role of autophagy in tumour biology. [less ▲]

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See detailComplete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis.
Schmitz, Martine UL; Grignard, Gerard; Margue, Christiane UL et al

in International Journal of Cancer (2007), 120(6), 1284-92

The EGF/IGF growth factors are potent mitogens that regulate cell proliferation and cell survival and are involved in prostate cancer development. Using laser microdissection technology and real-time PCR ... [more ▼]

The EGF/IGF growth factors are potent mitogens that regulate cell proliferation and cell survival and are involved in prostate cancer development. Using laser microdissection technology and real-time PCR, together with immunohistochemistry, we have explored the growth factor and integrin dependent PI3-kinase/PTEN/Akt signalling pathway in prostate cell lines and tumour samples by analysing EGF-R, IGF1-R, ILK, beta3 integrin, PTEN and p-Akt protein expression. We provide evidence that loss of PTEN expression rather than upregulated EGF/IGF1 receptor expression was responsible for increased p-Akt in neoplastic prostate cells. We therefore compared PTEN expression in patient biopsies at first time diagnosis recruited prospectively (Study I, 112 patients) and patients with confirmed metastasis recruited retrospectively from the Luxembourg cancer registry (Study II, 42 patients). In Study I, loss of PTEN expression at first time diagnosis was found in 26 of 112 patients (23%). In Study II, 25 of the 42 patients (59%) with lymph node metastasis had complete loss of PTEN expression in both the neoplastic glands of the prostate and the invasive prostate cancer cells in the lymph node, and of these 13 (52%) exhibited already loss of PTEN expression at first diagnosis. These findings demonstrate that loss of PTEN expression is an important factor in progression towards metastatic disease and could potentially serve as an early prognostic marker for prostate cancer metastasis. [less ▲]

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