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
Sign In
Advertise with Us
Technopath Clinical Diagnostics - An LGC Company

Logos Biosystems

Logos Biosystems is the life science solutions of Aligned Genetics, Inc., dedicated to the development and commercial... read more Featured Products: More products

Download Mobile App


ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.

Tumor Suppressor Adenomatous Polyposis Coli Regulates T Lymphocyte Migration

By LabMedica International staff writers
Posted on 20 Apr 2022
Print article
Image: The LUNA-FL Dual Fluorescence Cell Counter (Photo courtesy of Logos Biosystems)
Image: The LUNA-FL Dual Fluorescence Cell Counter (Photo courtesy of Logos Biosystems)

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease that often results from germline mutations in the adenomatous polyposis coli (APC) gene, a tumor suppressor and polarity regulator. APC protein regulates the Wnt/β-catenin signaling pathway as a component of the β-catenin destruction complex.

The key role of immunity in human colorectal carcinoma was underscored by the correlation between the type and frequency of infiltrating T lymphocytes and favorable patient prognosis. Once activated in lymph nodes, lymphocytes go through bloodstream recirculation and adhesion-dependent trans-endothelial migration to finally invade tumor tissues, where they execute their effector functions to eliminate tumor cells.

Cellular Biologist at the Institut Pasteur (Paris, France) and their colleagues recruited seven FAP patients and their respective sex-, age-, and ethnicity-matched healthy donors. Peripheral blood mononuclear cells were purified from FAP patients or healthy donors by Ficoll-Hypaque centrifugation and activated. Cell counts, viability and size were assessed every two days (up to day 12) by a LUNA-FL Dual Fluorescence Cell Counter, after cell staining with acridine orange/propidium iodide mixture (Logos Biosystems, Villeneuve d’Ascq, France).

At day 5, CD4 T cells were purified using positive magnetic sorting (Miltenyi Biotec, Bergisch Gladbach, Germany) and CD8 T cells recovered from the non-retained population. Other procedures carried out included siRNA transfections, chemotaxis studies, migration in microchannels, cell migration in 3D collagen matrices, cell migration in 3D collagen matrices, fluorescent microscopy with mages were acquired with an LSM700 confocal microscope (Carl Zeiss, Oberkochen, Germany).

The investigators unveiled that T cells from FAP patients carrying APC mutations display impaired adhesion and motility in constrained environments. They further dissected the cellular mechanisms underpinning these defects in APC-depleted CEM T cell line that recapitulate the phenotype observed in FAP T cells. They found that APC affects T cell motility by modulating integrin-dependent adhesion and cytoskeleton reorganization. Hence, APC mutations in FAP patients not only drive intestinal neoplasms, but also impair T cell migration, potentially contributing to inefficient antitumor immunity.

Marta Mastrogiovanni, MSc, PhD candidate and lead author or the study, said, “In order to move along blood vessel walls, cross them and reach the tumor to be infiltrated, healthy lymphocytes change their morphology. Something akin to a large adhesive foot, supported by the lymphocyte's cytoskeleton, grows longer in the direction of migration. This polarization is essential for movement in the right direction. In mutated lymphocytes, the microtubules making up the cytoskeleton are disorganized and there are fewer adhesion proteins. The cells lose their polarity and their 'muscles'.”

The authors concluded that their data provides the first evidence that APC orchestrates the coupling of cytoskeletal-mediated forces and integrin-dependent adhesion necessary for T cell migration as physiologically occurs across endothelial barriers, lymphoid organs, inflamed tissue and tumors. Consequently, APC defects may impair immune surveillance and effector functions of T cells, thus favoring tumorigenesis initiated by defects in epithelial cell differentiation in FAP patients. The study was published on April 13, 2022 in the journal Science Advances.

Related Links:
Institut Pasteur 
Logos Biosystems
Miltenyi Biotec
Carl Zeiss

Gold Supplier
Chemistry Analyzer
DP0150 Pulse 150
Microplate Reader
Microplate Washer

Print article


Clinical Chem.

view channel
Image: The analysis pipeline used to investigate associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease (Photo courtesy of University College London)

Lipid Measurements Show Potential as Alzheimer’s Disease Biomarkers

Brain changes accompanying ageing are varied and can include pathologies that lead to cognitive impairment, the commonest of which is Alzheimer’s disease (AD). Identifying blood-based signatures of brain... Read more

Molecular Diagnostics

view channel
Image: Researchers have identified 10 new genes linked with hearing loss (Photo courtesy of 123rf.com)

Newly Identified Genes May Help to Screen and Treat Individuals with Hearing Loss

A massive genome-wide association study (GWAS) identified 10 novel gene loci associated with hearing loss, which may aid in screening and treating the disorder. Hearing loss is one of the top contributors... Read more


view channel
Image: The CS-2500 analyzer features pre-analytic sample checks and four detection methods simultaneously on a single platform – coagulation end-point, chromogenic kinetic analysis, turbidimetric immunoassay and automated platelet aggregation (Photo courtesy of Sysmex)

Microvascular/Endothelial Dysfunction Contributes to Post-COVID Syndrome Pathogenesis

Post-COVID syndrome (PCS) or Long-COVID is an increasingly recognized complication of acute SARS-CoV-2 infection, characterized by persistent fatigue, reduced exercise tolerance chest pain, shortness of... Read more


view channel
Image: Sales of lateral flow assays in clinical testing are expected to register a CAGR of 5% through 2032 (Photo courtesy of Pexels)

Global Lateral Flow Assays Market to Surpass USD 11.5 Billion by 2032 Due to Evolving Applications

The global lateral flow assays market was valued at USD 7.2 billion in 2021 and is projected to register a CAGR of 4.7% during 2022-2032 to surpass USD 11.7 billion by the end of 2032, driven by the growing... Read more
Copyright © 2000-2022 Globetech Media. All rights reserved.