New micro-platform reveals cancer cells' natural behavior

September 19, 2018, Hokkaido University
New micro-platform reveals cancer cells’ natural behavior
Fluorescence images of pancreatic cancer micro-tumors after overnight culturing. Papillary structures pile up on micro-attachment sites (diameter 30µm), with numerous cells visible per patch. The rightmost micro-tumor has extended over two attachment sites. Nuclei, actin filaments, and microtubules are labeled with blue, green and red fluorescent markers respectively. Credit: Miyatake Y. et al., Scientific Reports, September 19, 2018

A new cell culture platform allows researchers to observe never-before-seen behaviors of live cancer cells under the microscope, leading to explanations of long-known cancer characteristics.

The easy-to-produce platform developed by Hokkaido University researchers offers cancer cells micro-scale attachment sites that elicit never-before-seen behaviors highly relevant to cancer's clinical properties. The observation of these behaviors shed light on the mechanisms behind well-known properties of pancreatic cancer, one of the most lethal malignant tumors, and may lead to the identification of new treatment targets.

"Cancer studies so far either use cell cultures in which cancer cells don't necessarily behave naturally, or tissue samples that don't allow live observation. So there is a big gap in our knowledge of how cancer cells actually behave," says Assistant Professor Yukiko Miyatake, who led the study and focuses on cancer development mechanisms. To close this gap, she teamed up with Associate Professor Kaori Kuribayashi-Shigetomi who specializes on micro-nano-scale bio-engineering.

Together they created a new cell culture substrate from a coated glass slide with etched islands of 30µm diameter. For , this is just enough space for one or two to attach. But when the researchers seeded them with pancreatic cancer cells (although they also tried other cancer cells with similar results) and incubated them overnight, the cells self-organized into micro-tumors that could move in a concerted way, as if it were one organism. Precursors to this turned out to be papillary structures that accommodate 4 or more cells by cell-in-cell invasion. This process, called entosis, is so far known only as a step in cell degradation. Here, the incorporated cells remained alive and, to their surprise, the incorporation was reversible.

New micro-platform reveals cancer cells’ natural behavior
Micro-patterned plate used for the study. The dish has a diameter of 40mm, the square glass slide an edge length of 20mm. The picture on the right shows micro-tumors extending over multiple micro-attachment sites. Credit: Hokkaido University

When they treated the micro-tumors with the widely used anti-cancer agent Nocodazole, the micro-tumor disintegrated, but the now-detached cells survived. Moreover, the researchers observed the micro-tumors "fishing" for surrounding and ingesting them, in the process releasing chemical markers typical for dead . These markers ended up on the ' surfaces, presumably masking them and enabling them to evade the immune system's .

Striving to reduce the suffering cancer causes, Miyatake says: "I hope this easy and low-cost technique will find widespread adoption. If the discoveries made during these first observations are physiologically or pathologically relevant phenomena, many more new hints may be gleaned for the development of more effective treatment approaches."

In the newly developed culture system, the pancreatic cancer cells (PDAC) self-organized and anchored to the micro-scale islands. Anchorage-dependent pancreatic cancer micro-tumors showed morphological polarity and motility. Arrows indicate presumed direction of movement. Credit: Miyatake Y. et al., Scientific Reports, September 19, 2018

Explore further: Reducing cholesterol could enhance T-cell cancer immunotherapy

More information: Yukiko Miyatake et al. Visualising the dynamics of live pancreatic microtumours self-organised through cell-in-cell invasion, Scientific Reports (2018). DOI: 10.1038/s41598-018-32122-w

Related Stories

Reducing cholesterol could enhance T-cell cancer immunotherapy

May 16, 2018
Cleveland Clinic researchers have demonstrated for the first time that lowering blood cholesterol levels could enhance the success of a specific type of T-cell immunotherapy in fighting cancer.

Study reveals new mechanism used by cancer cells to disarm attacking immune cells

November 20, 2017
A new study by researchers at The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute (OSUCCC - James) identifies a substance released by pancreatic cancer cells that protects ...

Researchers find novel way to induce pancreatic cancer cell death

April 10, 2017
Pancreatic cancer, most frequently pancreatic ductal adenocarcinoma (PDAC), is the most lethal and aggressive of all cancers. Unfortunately, there are not many effective therapies available other than surgery, and that is ...

Researchers advocate for single-cell diagnostics for breast cancer

October 24, 2017
Women diagnosed with breast cancer may benefit from having the molecular subtype of different cells within their tumors identified, argue two researchers in an opinion article published October 24 in the journal Trends in ...

Combination immunotherapy targets cancer resistance

November 22, 2017
Cancer immunotherapy drugs have had notable but limited success because in many cases, tumors develop resistance to treatment. But researchers at Yale and Stanford have identified an experimental antibody that overcomes this ...

Research discovers potential new Rx target for colon cancer

September 12, 2017
Genetic research conducted at LSU Health New Orleans School of Medicine and Stanley S. Scott Cancer Center demonstrated for the first time that a novel protein can cause normal cells in the lining of the colon to become malignant, ...

Recommended for you

A bad influence—the interplay between tumor cells and immune cells

October 16, 2018
Research at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) yielded new insights into the environment surrounding different types of lung tumors, and described how these complex cell ecosystems may in turn ...

Student develops microfluidics device to help scientists identify early genetic markers of cancer

October 16, 2018
As anyone who has played "Where's Waldo" knows, searching for a single item in a landscape filled with a mélange of characters and objects can be a challenge. Chrissy O'Keefe, a Ph.D. student in the Department of Biomedical ...

Technique to 'listen' to a patient's brain during tumour surgery

October 16, 2018
Surgeons could soon eavesdrop on a patient's brain activity during surgery to remove their brain tumour, helping improve the accuracy of the operation and reduce the risk of impairing brain function.

Researchers elucidate roles of TP63 and SOX2 in squamous cell cancer progression

October 16, 2018
Squamous cell carcinomas (SCCs) are aggressive malignancies arising from the squamous epithelium of various organs, such as the esophagus, head and neck, lungs, and skin. Previous studies have demonstrated that two master ...

Function of neutrophils during tumor progression unraveled

October 15, 2018
Researchers at The Wistar Institute have characterized the function of neutrophils, a type of white blood cells, during early stages of tumor progression, showing that they migrate from the bone marrow to distant sites and ...

Delving where few others have gone, leukemia researchers open new path

October 15, 2018
A Wilmot Cancer Institute study uncovers how a single gene could be at fault in acute myeloid leukemia (AML), one of the deadliest cancers. The breakthrough gives researchers renewed hope that a gene-targeted therapy could ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.