biostudies-literatureDi Agostino SMinistero dell'Università e della RicercaMinistero dell'Università e della RicercaNextGenerationEU247https://www.ebi.ac.uk/biostudies/studies/S-EPMC12372361biostudies-literatureUnknown44(1)The tumor microenvironment (TME) plays a pivotal role in the development and progression of colorectal cancer (CRC), yet the complex crosstalk among its components remains incompletely understood. Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) have emerged as key regulators of CRC progression, but their specific contributions, particularly given their heterogeneity, are not fully elucidated. This study identifies podoplanin (PDPN), a transmembrane glycoprotein enriched in CAFs, as highly expressed in the CRC TME, in particular surrounding the tumor, and associated with macrophage infiltration and cancer progression. We performed mass spectrometry-based proteomic analysis on matched CRC and adjacent normal tissues from patients to identify altered signaling patJournal of experimental & clinical cancer research : CRProteomic profiling identifies a stromal TGF-β1/podoplanin axis as a driver of colorectal cancer progression.PMC123723612022CMTZNHCurro GCuda GDi Agostino SRanieri GAmmendola MAprigliano EUrlandini LConforti FGaspari MZuccala VIeni ALa Padula DAbbonante VCernaro VGabriele CVescio FSacconi AParrotta ELofaro DRago VAlibrandi AfalseProteomic profiling identifies a stromal TGF-β1/podoplanin axis as a driver of colorectal cancer progression.The tumor microenvironment (TME) plays a pivotal role in the development and progression of colorectal cancer (CRC), yet the complex crosstalk among its components remains incompletely understood. Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) have emerged as key regulators of CRC progression, but their specific contributions, particularly given their heterogeneity, are not fully elucidated. This study identifies podoplanin (PDPN), a transmembrane glycoprotein enriched in CAFs, as highly expressed in the CRC TME, in particular surrounding the tumor, and associated with macrophage infiltration and cancer progression. We performed mass spectrometry-based proteomic analysis on matched CRC and adjacent normal tissues from patients to identify altered signaling pat2025-01-01T00:00:00Z2025 Aug2026-05-08T10:48:02.042Z2026-04-07T23:47:44.08ZS-EPMC123723614084202710.1186/s13046-025-03496-3