SQUISHY CANCER CELLS NANOTECHNOLOGY: Atomic force microscopy pinpoints cancer cells by their softness
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TOMIC FORCE MICROSCOPY (AFM) can be used to distinguish metastatic cancer cells from normal cells on the basis of stiffness rather than shape, according to a new report from researchers at the University of California, Los Angeles. The cancer cells are significantly squishier than the normal cells, and the method promises to improve cancer diagnostics. Chemistry professor James K. Gimzewski, pathology professor Jianyu Rao, and coworkers use AFM to measure the stiffness of cells in fluids taken from the body cavities of patients with suspected metastatic lung, breast, or pancreatic cancer (Nat. Nanotechnol., DOI: 10.1038/ nnano.2007.388). Any cancer cells found in these fluid samples will be metastatic because they have escaped the primary tumor. The researchers find that metastatic cancer cells are nearly four times softer than normal cells. “These results, which show extreme softness of metastatic cancer cells from patients, are an important addition to a rapidly growing literature on the distinctiveness of elasticity of cells and matrix in both health and disease,” says Dennis E. Discher, a professor of molecular and cell biophysics at the University of Pennsylvania who studies mechanical properties of cells. Cancer cells are usually identified by their shape and
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by antibody staining. In fluid samples, however, the cells that line body cavities often have enlarged nuclei and rounded shapes similar to those of cancer cells. It takes years to develop the skill to distinguish normal from cancer cells by looking at their morphology and analyzing results from staining, Gimzewski says. “We are using a quantitative test that is not dependent on having a person trained as a pathologist.” Rao and Gimzewski’s team identified cancer cells that appeared normal on the basis of their morphology. Although the team has not yet studied primary tumor cells, Rao expects that primary tumor cells that are destined to spread to other parts of the body will prove to be softer than ones that will stay put. He hopes that the AFM measurements, therefore, will help pathologists predict which patients need to be treated more aggressively. Currently, pathologists can’t reliably predict which patients will develop metastatic cancer. More work is needed to prove that these measurements benefit patients, but Rao anticipates a day when all pathology labs will use such technology. Because the AFM instrument is mounted on an inverted optical microscope, Gimzewski notes, fluorescence measurements and AFM measurements could be done on the same instrument. “If we can demonstrate the test provides diagnostic information critical for patient care, I don’t think it will be difficult to convince people to set this system up in the hospital setting,” Rao says.—CELIA ARNAUD
Pathologists usually distinguish cancer cells and normal cells by their shapes. In this image, metastatic cancer cells are labeled in red.
DRUG DISCOVERY Collaborations set between European biotechs and pharma giants antibody discovery programs. During a conference call with securities analysts, MorphoSys CEO Simon Moroney would not elaborate on specific areas of investigation but did say that MorphoSys’ own projects, particularly in rheumatoid arthritis, would be unaffected. Analysts seemed enthusiastic about the deal, which DZ Bank’s Patrick Fuchs MO RP HOSYS
Two small European firms are the latest biotech specialists to benefit as large pharmaceutical companies seek innovative ways to fill their product pipelines. In the larger deal, which could be worth more than $1 billion, Munichbased MorphoSys has formed a 10-year alliance with Novartis to develop therapeutic antibodies. MorphoSys will receive more than $600 million from Novartis over 10 years for R&D funding and technology access, and future royalty payments could add more. The two companies began working together in 2004 to develop MorphoSys’ HuCAL human antibody technology. Now, Novartis will accelerate its plan to install the HuCAL technology at its research sites. Over the lifetime of the agreement, the parties will double their therapeutic
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termed “very elegant financially and strategically.” The alliance is “a transforming deal for MorphoSys,” Moroney said, giving his company more resources to power its own corporate development and reduce its reliance on fee-for-service discovery deals. In the other deal, Addex Pharmaceuticals, a Swiss company specializing in allosteric modulation, which centers on tuning receptor-drug interactions, has entered an exclusive collaboration with Merck & Co. to develop a new class of orally available drugs. Initial projects will focus on Parkinson’s disease. Addex will receive $3 million up front and is eligible for up to $106.5 million in research, development, and regulatory milestone payments for the first product developed for multiple indications.—PATRICIA SHORT
