title: Friend or foe? The tumour microenvironment dilemma in colorectal cancer.
abstract: The network of bidirectional homotypic and heterotypic interactions established among parenchymal tumour cells and surrounding mesenchymal stromal cells generates the tumour microenvironment (TME). These intricate crosstalks elicit both beneficial and adverse effects on tumour initiation and progression unbalancing the signals and responses from the neighbouring cells. Here, we highlight the structure, activities and evolution of TME cells considering a novel colorectal cancer (CRC) classification based on differential stromal composition and gene expression profiles. In this scenario, we scrutinise the molecular pathways that either change or become corrupted during CRC development and their relative prognostic value. Finally, we survey the therapeutic molecules directed against TME components currently available in clinical trials as well as those with stronger potential in preclinical studies. Elucidation of dynamic variations in the CRC TME cell composition and their relative contribution could provide novel diagnostic or prognostic biomarkers and allow more personalised therapeutic strategies.
authors.affiliation: Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy; present address: Institute for Stem-cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Casa Sollievo della Sofferenza-IRCCS, 71013 San Giovanni Rotondo (FG), Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Colangelo
authors.affiliation: Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Polcaro
authors.affiliation: Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Muccillo
authors.affiliation: Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Agostino
authors.affiliation: Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Rosato
authors.affiliation: Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ziccardi
authors.affiliation: Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Lupo
authors.affiliation: Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo (FG), Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mazzoccoli
authors.affiliation: Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy. Electronic address: sabatino@unisannio.it.
authors.forename: Lina
authors.initials: L
authors.lastname: Sabatino
authors.affiliation: Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy. Electronic address: colantuoni@unisannio.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Colantuoni
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology; D011379:Prognosis; D059467:Transcriptome / Q000502:physiology; D059016:Tumor Microenvironment / Q000502:physiology*
keywords: Cancer-associated fibroblasts; Cell-cell communications; Colorectal cancer; Immune cells; Stromal cells; Tumour microenvironment