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Researchers Advance Cell Stretching Technology for Cancer Detection

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NEW YORK (360Dx) – A team from Germany's Leipzig University has published early data that suggests that a technology called the optical stretcher — which uses lasers to capture and deform individual cells — might offer a way to detect early cancers by picking up physical changes in cells that indicate a malignant transformation.

Studying cells from oral squamous cell carcinomas, investigators observed that in addition to being softer than normal cells, cancers cells, at least in this type of tumor, also contracted more quickly than their benign counterparts after being stretched and then released.

The authors, who published their findings in the journal Convergent Science Physical Oncology this week, wrote that their interest in looking for this type of mechanical sign of cancer in OSCC is because it is the most common head and neck cancer, but is often diagnosed in later stages.

One of the Leipzig investigators, Josef Käs, developed the optical stretcher technology used in the study with a former postdoc, Jochen Guck. The technique uses lasers to deform individual cells passing through a microfluidic channel, offering a quantitative readout on the physical and mechanical properties of cells — how soft or malleable they are, how resilient, or how stiff.

In an email, study author Jörg Schnauß wrote that though he and his colleagues are one of the main groups investigating the technology, but other research teams are also studying it, not just in cancer, but as a potential way to distinguish any number of diseases based on changes in the physical and mechanical properties of cells.

A company, called RS Zelltechnik, has also been spun out from the group's Leipzig lab to supply these investigations, Schnauß added.

For the majority of the diagnostics community, efforts to develop cancer detection and diagnosis tools are tied to genomic and other molecular technologies — looking for biomarkers on the molecular level that can identify cancer cells, or fragments of cancer DNA.

The Leipzig team views their work with the optical stretcher technology as potentially offering a much simpler tool, perhaps with added value to protein or DNA-based tests.

"Although [molecular] markers are very valuable tools in diagnosing cancer, we think along a completely different line," Schnauß wrote in his email. Dealing with simple mechanics removes the complexity of molecular analyses, and there is no need to address issues like variability between different disease types or states.

"With our technique, we are more or less ignoring the molecular diversity in cells in general and of cancer cells in particular. We are 'simply' testing their material properties and how they are altered under pathological changes," Schnauß said.

Schnauß's group applied the optical stretcher technology to two goals — first studying OSCC patient samples and comparing them to normal controls, and then analyzing how cells from a primary sample compare to those from cultured cell lines.

According to the authors, an analysis of close to 1,500 primary OSCCs and about 350 normal control samples showed that cancer samples were significantly more deformable than normal cells. OSCC cells deformed by 2.9 percent on average, while cells from healthy oral mucosa, deformed only by about 1.9 percent.

In addition, the team wrote, cancer cells also showed more elasticity than normal cells, displaying a " continuous return towards their initial shape … while healthy cells quickly plateau at still high deformability values."

Schnauß and his colleagues also wrote that their results offer evidence to help resolve an ongoing debate about what relative softness and elasticity in cancer cells reflects in terms of how cancer grows and spreads.

Some have argued that cell softening may reflect tumor progression, and the advancement of more serious metastatic disease, rather than being a marker of earlier tumor development.

But because the Leipzig authors studied cells removed from primary, non-metastatic tumors, they argued that their results support the idea that changing mechanical properties may be reflective more of the transformation from benign to malignant tissue than of increasing aggressiveness of tumor.

This would bode well toward the goal of applying optical stretching to detecting primary cancers, especially trying to diagnose them earlier in their development.

The group also studied the deformability of cells from primary samples compared to those from cultured cell lines to try to quantify how cell culture might confound efforts to compare the physics of malignant and benign samples.

As they hypothesized, the investigators observed that long culturing appears to lead to softer cells on average, suggesting that using cell lines could confound efforts to develop mechanics-based diagnostics.

"To establish a serious diagnostic tool for direct application in the medical practice, the use of primary samples without cultivation is strongly recommended," the authors wrote.

Schnauß wrote that the group's goal is to continue to study how the optical stretcher might simplify or improve diagnosis in OSCC and in other cancers, potentially serving as a more objective, more quantitative measure of the presence of cancer than current pathologic methods that rely on the subjective visual inspection of a sample.

Cervical cancer and breast cancer are two other areas that the team is applying the stretcher to right now, he added.

In oral cancer, the team is planning to move from studying sample from patients with a known OSCC, to trying to establish whether the technology can detect early signals of cancer in cases where there is not already a clear diagnosis.

They also hope to study whether biopsy tissue is needed, or if the technology could be applied to detect cancer cells noninvasively, in saliva samples.