We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
PURITAN MEDICAL

THERMO FISHER SCIENTIFIC

Thermo Fisher Scientific provides analytical instruments, lab equipment, specialty diagnostics, reagents and integrat... read more Featured Products: More products

Download Mobile App




Melanoma Test Offers Reassurance of Low Risk of Cancer Spread

By LabMedica International staff writers
Posted on 25 Jan 2022
Cutaneous melanoma is an aggressive form of skin cancer with an increasing worldwide incidence, particularly in the younger population. More...
Although treatment for patients with metastatic melanoma has improved remarkably in the last decade, principally with targeted therapies and immune checkpoint modulators, there are still no consistently beneficial treatments for patients with metastatic disease.

AMBRA1 is a scaffold protein with key roles in autophagy, cell survival and proliferation. AMBRA1 promotes autophagy through initiation of autophagosome formation, and mitophagy-mediated clearance of damaged mitochondria. Melanoma cells can influence the tumor microenvironment through secretion of growth factors, including transforming growth factors α and β (TGF-α, TGF-β).

Clinical Scientists at Newcastle University (Newcastle, UK) and AMLo Biosciences Limited (Newcastle upon Tyne, UK) and their colleagues evaluated the potential contribution of melanoma paracrine transforming growth factor (TGF)-β signaling to the loss of AMBRA1 in the epidermis overlying the primary tumor and disruption of epidermal integrity. Immunohistochemistry was used to analyze AMBRA1 and TGF-β2 in a cohort of 109 AJCC all-stage melanomas, and TGF-β2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analyzed in a cohort of 42 melanomas, with TGF-β2 signaling evaluated in primary keratinocytes.

The investigators performed semiquantitative immunohistochemistry for or AMBRA1, TGF-β2, TGF-β3, claudin-1 or AMLo expression. Claudin-1 expression was quantified by H-score using Aperio ImageScope (Leica Biosystems, Nussloch Germany). Western blotting was generated and visualized using enhanced chemiluminescence (Bio-Rad, Watford, UK). Total RNA was isolated from cell pellets and reverse transcribed using an AMV Reverse Transcriptase kit (Promega, Madison, WI, USA) or High Capacity Reverse Transcription Kit (Thermo Fisher Scientific, Waltham MA, USA).

The scientists reported that increased tumoral TGF-β2 was significantly associated with loss of peritumoral AMBRA1, ulceration, AMLo high-risk status and metastasis. TGF-β2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes. Importantly, they showed loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression, parakeratosis and cleft formation in the dermoepidermal junction.

Penny E. Lovat, PhD, Professor of Cellular Dermatology and senior author of the study, said, “Like mortar and bricks holding together a wall, AMBRA1, Loricrin and Claudin 1 are all proteins key to maintaining the integrity of the upper layer of the skin. When these proteins are lost gaps develop, like the mortar crumbling away in the wall. This allows the tumor to spread and ultimately ulcerate which we know is a process associated with higher risk tumors. Our new understanding of this biological mechanism underpins the test we have available.”

The authors concluded that their data suggested a paracrine mechanism whereby melanoma secretion of TGF-β2 causes peritumoral loss of AMBRA1 and reduced epidermal integrity facilitating erosion of the epidermis and tumor ulceration. Targeting TGF-β2 signaling may therefore represent a novel adjuvant treatment strategy for high-risk early-stage tumors with loss of epidermal AMBRA1. The study was published on January 13, 2022 in the British Journal of Dermatology.

Related Links:
Newcastle University
AMLo Biosciences Limited
Leica Biosystems
Bio-Rad
Promega
Thermo Fisher Scientific



Gold Member
Troponin T QC
Troponin T Quality Control
3-Part Differential Hematology Analyzer
Swelab Alfa Plus Sampler
New
Rapid Test Reader
DIA5000
New
Automated PCR Setup
ESTREAM
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








DIASOURCE (A Biovendor Company)

Channels

Hematology

view channel
Image: CitoCBC is the world first cartridge-based CBC to be granted CLIA Waived status by FDA (Photo courtesy of CytoChip)

Disposable Cartridge-Based Test Delivers Rapid and Accurate CBC Results

Complete Blood Count (CBC) is one of the most commonly ordered lab tests, crucial for diagnosing diseases, monitoring therapies, and conducting routine health screenings. However, more than 90% of physician... Read more

Immunology

view channel
Image: A simple blood test could replace surgical biopsies for early detecion of heart transplant rejection (Photo courtesy of Shutterstock)

Blood Test Detects Organ Rejection in Heart Transplant Patients

Following a heart transplant, patients are required to undergo surgical biopsies so that physicians can assess the possibility of organ rejection. Rejection happens when the recipient’s immune system identifies... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.