Published in Science Advances. Kidney cells carry 30 to 200 nm cancer derived vesicles across a filtration barrier long thought to stop particles above roughly 7 nm, by a route called transcytosis. The effect held in mouse models of brain, lung, and pancreatic cancer, and strengthens the scientific basis of Craif's urinary microRNA testing.

A multicenter research group in Japan has shown that small extracellular vesicles, including exosomes secreted by cancer tissue, are excreted into urine by active work of the kidney, and has identified the mechanism. In mouse models, cancer derived exosomes from tumors far from the kidney, in the brain, lung, and pancreas, tended to be more concentrated in urine than in blood, which the group reports as a first. The findings were published in Science Advances on February 20, 2026, local time.

The group was led by Professor Takao Yasui and Assistant Professor Taiga Ajiri of the School of Life Science and Technology at the Institute of Science Tokyo, both technical advisors to bio AI company Craif Inc. (headquarters: Shinjuku, Tokyo; Representative Director and CEO: Ryuichi Onose), with researchers from the University of Tokyo and Nagoya University.

The result speaks to the objection most often raised against urine as a cancer sample. Craif has previously reported research findings that analysis of urinary extracellular vesicles and microRNA is highly effective for the early detection of 10 cancer types including pancreatic cancer. What stayed unclear was whether extracellular vesicles secreted by cancer itself actually reach urine, and if so in what quantity and by what mechanism.

The sticking point was size. The mesh of the glomerulus, the kidney's filter, is said to be about 6 to 7 nm, while extracellular vesicles such as exosomes secreted by cancer cells are far larger at 30 to 200 nm. How those vesicles break through that size barrier and end up in urine had gone unexplained for years.

What the study found

• How cancer derived vesicles get past the kidney's size barrier: the glomerular filtration barrier generally excludes molecules larger than about 6 to 7 nm, and the study resolves the long standing puzzle of why extracellular vesicles such as cancer derived exosomes, roughly 100 nm in size within a 30 to 200 nm range, appear in urine at all.
• An active transport route, transcytosis: kidney cells take up cancer derived particles and expel them on the far side, carrying them into urine.
• More concentrated in urine than in blood: in a lung cancer mouse model, concentrations of particles released by the tumor were higher in urine than in blood.
• Across a broad range of cancer types: excretion of cancer derived extracellular vesicles into urine was confirmed consistently for cancers arising at sites remote from the urinary tract, including brain tumors, lung cancer, and pancreatic cancer.

How the study was done

In conventional liquid biopsy blood has played the lead role, and urine has generally been seen as convenient but less accurate than blood. The main reason was the belief that the kidney's fine filter, the glomerulus, cannot pass particles above a certain size, exosomes released by cancer cells among them.

When the research group ran tracking experiments using cancer cells labeled with guide RNA and luminescent proteins, it found that cancer derived particles circulate in the bloodstream and are released into urine by way of transcytosis, an intracellular transport mechanism.

Validation in cancer models at multiple sites, lung and pancreas, showed that in many cases cancer derived extracellular vesicles such as exosomes are detected in greater quantity, or at higher concentration, in urine than in blood.

The work presents scientific grounds for urinary extracellular vesicles serving as reliable cancer biomarkers. The expectation is that it accelerates development of next generation cancer diagnostics using urine samples, which are less invasive and simpler to collect than a blood draw.

These findings strongly support the scientific validity of Craif's urinary microRNA based early cancer detection technology and show that urine is an extremely important source of biomarker information for next generation liquid biopsy.

Why it matters

In Japan, one in two people will develop cancer, and the importance of early detection has never been greater. Invasive methods such as endoscopy and blood draws place a mental and physical burden on the person being screened, and that burden has been a barrier to regular screening.

By clarifying the scientific basis for detecting cancer from urine with high accuracy, this work sharply raises the reliability of urine testing as a painless, noninvasive first line screen. The expectation is that opportunities for cancer screening widen, and that the benefit of very early detection and early treatment reaches more people.

Publication information

Journal: Science Advances

Title: Glomerular routing of tumor-derived extracellular vesicles substantiates urinary biopsy

Authors: Shota Kawaguchi, Taiga Ajiri, Rina Mitsuya, Reiko Tsuchiya, Koki Kunitake, Yoshikazu Tanaka, Takeshi Yokoyama, Kiichi Sato, Yusuke Sato, Zetao Zhu, Kunanon Chattrairat, Yasuko Kobayashi, Kimiko Inoue, Keisuke Imaeda, Kosei Ueno, Sou Ryuzaki, Akira Kato, Yasuyuki Kimura, Atsushi Natsume, Ryosuke Kojima, and Takao Yasui

DOI: 10.1126/sciadv.aeb0555

Key terms

• Extracellular vesicles and exosomes: small sac like particles secreted by cells and used for signaling within the body. Exosomes, one type of extracellular vesicle, are rich in substances such as microRNA and carry information useful for diagnosing cancer.
• Glomerulus: a cluster of capillaries inside the kidney that performs the first step of filtering blood to make urine. It has three layers, endothelial cells, basement membrane, and podocytes, and works as a filter that strains waste products and excess water out of blood. That filter is thought not to pass molecules above a certain size.
• Transcytosis: the process by which a substance passes through a cell. A molecule or particle is taken into the cell, moves through it, and is released on the other side. Large particles that cannot pass through the filter can still move across, because the cell carries them to the far side.
• Liquid biopsy: testing for disease, including cancer, using body fluids such as blood or urine. It is less invasive than cutting out tissue. Liquid biopsy from a urine sample involves no incision and no pain, which makes it the least invasive form of testing.

About Craif

Craif is a bio AI startup founded in 2018 that works on the early detection of cancer. It combines AI with NANO IP (NANO Intelligence Platform), its proprietary analytical platform for detecting a wide range of biomarkers, including DNA and microRNA, at high accuracy from body fluids such as urine, and develops tests intended to make very early cancer detection, early treatment, and early return to normal life possible. By bringing biotechnology and AI widely into society, Craif advances its vision of a society in which people live out their full natural lifespan.

Company details

Company name: Craif Inc.
Representative: Ryuichi Onose, Representative Director and CEO
Founded: May 2018
Business: research and development of next generation testing for the early detection of disease, with a focus on cancer, and for personalized medicine, and provision of miSignal, a urine based cancer risk test
Headquarters: THE PORTAL iidabashi B1F, 8-30 Shin-Ogawamachi, Shinjuku-ku, Tokyo

URL: https://craif.com/