Forskningsrapport från USA

Bloggen har fått mejl från 2 håll (tack Oscar &  Håkan) om en ny amerikansk studie. 4 forskare från Pennsylvania har studerat en lite ovanligare form av hudcancer.Merkel Cell Carcionoma (MCC) som tydligen uppkommer från ett virus när kroppens DNA av någon anledning blvit skadat. Viruset är döpt till Merkel cell polyomavirus (MCV) och upptäcktes 2008 av forskarna Patrick Moore och Yuan m kollegor. MCV gör oftast inget väsen av sig men när det sker för de olycksaligt drabbade är det brådis att agera då cancern som uppkommit är synnerligen aggresivt. 

Av den anledningen har det vuxit fram en kommersiell verksamhet som går ut på att undersöka hud hos de som är rädda för att ha viruset,det för att sätta in behandling innan viruset utvecklat en aggresiv cancer. Länk

Namnet Merkel Cell är taget efter dess upptäckare Johann Friedrich Sigmund Merkel, som strax innan sekelskiftet 1900 i sina studier om hudens olika lager gjorde upptäckten att vissa hudceller agerade som receptorer för tryck och skickade vidare sådana intryck till närliggande nerver.

Diagram of normal Merkel cells in the skin. Figure Copyright by Paul Nghiem, MD, PhD & Quade Medical Group.

Merkels cancer är ännu inte fullt kartlagd då forskarna haft svårt att lista ut dess uppkomst i alla delar.

Branschorganet Dermatology Times beskriver det såhär :

Merkel cell carcinoma (MCC) is a highly malignant form of skin cancer with a rather mysterious pathogenesis. However, new clues about the immune system response to MCC may be able to help guide future treatment strategies.

The rare nature of this disease, alongside its primary appearance in older adults, has made the development of MCC difficult to understand. In addition to the mysterious origins of this type of cancer, another characteristic that adds to questions about Merkel cell carcinoma is its ability to spontaneously regress in a surprising number of cases.

Så de 4 amerikanska forskarna i denna aktuella studie tar sig an ett angeläget problem med att försöka visa på just denna cancerns ursprungliga härkomst. Men till studien som är publicerad för 2 dagar sen och heter :

Merkel Cell Polyomavirus Large T Antigen Induces Cellular Senescence for Host Growth Arrest and Viral Genome Persistence through Its Unique Domain 

Published 20 January 2023

Abstract:

Senescent cells accumulate in the host during the aging process and are associated with age-related pathogeneses, including cancer. Although persistent senescence seems to contribute to many aspects of cellular pathways and homeostasis, the role of senescence in virus-induced human cancer is not well understood. Merkel cell carcinoma (MCC) is an aggressive skin cancer induced by a life-long human infection of Merkel cell polyomavirus (MCPyV). Here, we show that MCPyV large T (LT) antigen expression in human skin fibroblasts causes a novel nucleolar stress response, followed by p21-dependent senescence and senescence-associated secretory phenotypes (SASPs), which are required for MCPyV genome maintenance. Senolytic and navitoclax treatments result in decreased senescence and MCPyV genome levels, suggesting a potential therapeutic for MCC prevention. Our results uncover the mechanism of a host stress response regulating human polyomavirus genome maintenance in viral persistency, which may lead to targeted intervention for MCC.

Materials and Methods (urval)

4.9. Cell Proliferation Assay

Cells were plated on 6-well, TC plates (Thermo Scientific) at a confluency of approximately 30%, and they were incubated with 10% serum. After 24 h, cells were recorded using a phase holographic imaging system (HoloMonitor M4 laser microscope, Phase Holographic Imaging, Lund, Sweden). Images were recorded every 30 min for 48 h. Average cell proliferation was quantified using HStudio M4 software (version 2.7.1).

MCPyV LT expression has been shown to reduce cell proliferation through either the C-terminus or the MUR domain. To identify if cellular senescence was a potential cause of growth inhibition through the MUR domain, a HoloMonitor (PHI Lab), a non-invasive live-cell imager and counter was utilized. MCPyV LT-expressing cells proliferated slower than their MCPyV LTdMUR counterparts (Figure 4D). Additionally, the incorporation of 5-ethynyl-2′-deoxyuridine (EdU) by MCPyV LT-expressing cells was markedly reduced compared to the MCPyV LTdMUR mutant (Figure 4E and Figure S7). Knockdown of p21 in MCPyV LT-expressing cells reversed growth inhibition induced by MCPyV LT expression (Figure 4D,E). Although p21-dependent senescence often leads to G1 cell cycle arrest [1], our results indicate that MCPyV LT-mediated p21 activation mainly facilitated G2-arrested cellular senescence, negatively regulating cell growth.

(D) MCPyV LT restricts cell proliferation by inducing senescence. Non−invasive live cell imaging of transduced BJ−hTERT cells was conducted using a phase holographic imaging system (HoloMonitor M4) to measure cell proliferation rates.

I stycket Discussions avslutar man med följande :
Although whether latent viral infection can ultimately lead to oncogenesis by inducing host senescence and other stress environments needs further investigation, such cellular responses surely contribute to maintaining cellular homeostasis during virus infections. Our results uncover the mechanism of a host stress response in regulating human polyomavirus genome maintenance in a persistent viral infection, which may lead to targeted interventions for MCC.

Min kommentar

Som jag förstår det har forskarna hittat ett samband mellan åldrande celler (innan apoptosens slutskede) och tillfället de utsätts för "stress". Alltså när viruset aktiveras. Med benäget användande av HoloMonitor har de sett cellernas utveckling till stadiet de blir cancerogena. En viktig upptäckt de tror kan hävas genom att agera i cellernas apoptos blir min ytterst lekmannamässiga slutsats.

Ånyo visar sig HoloMonitor vara ypperlig för avancerad cancerforskning.

                                               Mvh the99

 

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