Bartak, M. | bioRxiv Science

bioRxiv2025

Fractionated radiation alters the extracellular matrix produced by muscle-invasive bladder cancer cells

Muscle-invasive bladder cancer (MIBC) is a prevalent disease that can be treated with radiotherapy, but has a poor prognosis. Radiation-induced extracellular matrix (ECM) remodelling and fibrosis can induce tumour resistance and recurrence, but has not been studied in MIBC. Here we aimed to characterise the impact of radiation on the ECM composition of MIBC. Materials and MethodsThree MIBC cell lines (T24, UMUC3, J82) were treated with fractionated radiation. We used proteomics to analyse the ECM composition produced by surviving cancer cells and immunofluorescence to investigate changes in the morphology and number of ECM fibres. We evaluated the RNA expression of identified ECM proteins (FN1, COL5A1, COL1A1, TNF6AIP6, FLG) in one cystectomy (TCGA-BLCA, n=397) and two radiotherapy (BC2001, n=313; BCON, n=151) cohorts. ResultsThere were 613 proteins affected by radiation (padj<0.05, fold change >2 or <-2), 68 of which were ECM-associated proteins. There was a general increase in proteases and protease regulators but heterogeneity across cell lines. Enrichment analysis showed ECM organisation was the primary pathway affected. Immunofluorescence confirmed radiation affected ECM structure, generally, reducing the number, length and width of fibres. High FN1, COL5A1, COL1A1, TNF6AIP6 and FLG mRNA levels were adverse prognostic markers in clinical cohorts. ConclusionRadiation alters the composition and structure of the ECM produced by MIBC. As a proof-of-concept, we showed the expression of radiation-affected ECM genes are prognostic markers in MIBC. Future studies should validate these radiation-induced ECM changes in clinical samples.

cancer biology↗

bioRxiv2024

Confirmation of Highly Pathogenic Avian Influenza (HPAI) H5N1 Associated with an Unexpected Mortality Event in South Polar Skuas (Stercorarius maccormicki) during 2023-2024 Surveillance Activities in Antarctica

From December 2023 to March 2024, a surveillance program to detect HPAI H5N1 was performed on Antarctica Territory, at Fildes Peninsula (King George Island, Maritime Antarctic), and James Ross Island. At Fildes Peninsula, samples from marine birds and mammals from four sampling locations were collected, based on their accessibility and the presence of animal colonies: Ardley Island, which presents a high concentration of Gentoo penguins (Pygoscelis papua); Ardley Cove were small groups of likely non-reproductive Chinstrap penguins (Pygoscelis antarcticus); Southern elephant (Mirounga leonina) and Weddell (Leptonycotes wedellii) seals haul-out sites; and, a nesting site of Southern giant petrels (Macronectes giganteus). On February 28th the surveillance group received a request for sample collection, due to the observation of deceased seabirds at James Ross Island in the area neighboring the Lachman lakes (63.7989 S, 57.8105 W). Six samples from five dead South polar skuas (Stercorarius maccormicki) were collected on March 3rd, 2024. All samples were collected adhering to the Antarctic Treaty guidelines. After collecting a total of 943 samples from Fildes Peninsula all results tested negative, and no individuals had clinical signs or behaviors compatible with HPAI. However, all samples from South polar skuas from James Ross Island were confirmed positive for HPAI H5N1 clade 2.3.4.4 by specific real-time RT-PCR reactions. These results confirmed the first mortality event registered in Antarctica (south of 60{degrees}S) caused by HPAI H5N1, in this case on South polar skuas. Further studies are needed to genetically characterize the virus and to better understand the role of skuas in the dynamics of viral dissemination in Antarctica.

microbiology↗