Landmark physical characterization of cancer cells completed

An enormous collaborative effort between a multitude of academic and research centers has characterized numerous physical and mechanical properties on one identical human cancer cell line. Their two-year cooperative study, published online in the April 26, 2013 journal Science Reports, reveals the persistent and agile nature of human cancer cells as compared to noncancerous cells. It also represents a major shift in the way scientific research can be accomplished.

Human breast cancer cells like these were used in the study. (Image created by Shyam Khatau/ Wirtz Lab)

Human breast cancer cells like these were used in the study. (Image created by Shyam Khatau/ Wirtz Lab)

The research, which was conducted by 12 federally funded Physical Sciences-Oncology Centers (PS-OC) sponsored by the National Cancer Institute, is a systematic comparison of metastatic human breast-cancer cells to non-metastatic breast cells that reveals dramatic differences between the two cell lines in their mechanics, migration, oxygen response, protein production and ability to stick to surfaces. They have also discovered new insights into how human cells make the transition from nonmalignant to metastatic, a process that is not well understood.

Denis Wirtz, a Johns Hopkins professor of chemical and biomolecular engineering with joint appointments in pathology and oncology who is the corresponding author on the study, remarked that the work adds a tremendous amount of information about the physical nature of cancer cells. “For the first time ever, scientists got together and have created THE phenotypic signature of cancer” Wirtz said. “Yes, it was just one metastatic cell line, and it will require validation with many other cell lines. But we now have an extremely rich signature containing many parameters that are distinct when looking at metastatic and nonmetastatic cells.”

Wirtz, who directs the Johns Hopkins Physical Sciences-Oncology Center, also noted the unique way in which this work was conducted: all centers used the same human cell line for their studies, which makes the quality of the results unparalleled. And, since human and not animal cells were used, the findings are immediately relevant to the development of drugs for the treatment of human disease.

“Cancer cells may nominally be derived from the same patient, but in actuality they will be quite different because cells drift genetically over just a few passages,” Wirtz said.  “This makes any measurement on them from different labs like comparing apples and oranges.” In this study, however, the genetic integrity of the cell lines were safeguarded by limiting the number times the original cell cultures could be regrown before they were discarded.

The nationwide PS-OC brings together researchers from physics, engineering, computer science, cancer biology and chemistry to solve problems in cancer, said Nastaran Zahir Kuhn, PS-OC program manager at the National Cancer Institute.

“The PS-OC program aims to bring physical sciences tools and perspectives into cancer research,” Kuhn said. “The results of this study demonstrate the utility of such an approach, particularly when studies are conducted in a standardized manner from the beginning.”

For the nationwide project, nearly 100 investigators from 20 institutions and laboratories conducted their experiments using the same two cell lines, reagents and protocols to assure that results could be compared. The experimental methods ranged from physical measurements of how the cells push on surrounding cells to measurements of gene and protein expression.

“Roughly 20 techniques were used to study the cell lines, enabling identification of a number of unique relationships between observations,” Kuhn said.

Wirtz added that it would have been logistically impossible for a single institution to employ all of these different techniques and to measure all of these different parameters on just one identical cell line. That means that this work accomplished in just two years what might have otherwise taken ten, he said.

The Johns Hopkins PS-OC made specific contributions to this work. Using particle-tracking microrheology, in which nanospheres are embedded in the cell’s cytoplasm and random cell movement is visually monitored, they measured the mechanical properties of cancerous versus noncancerous cells. They found that highly metastatic breast cancer cells were mechanically softer and more compliant than cells of less metastatic potential.

Using 3D cell culturing techniques, they analyzed the spontaneous migratory potential (that is, migration without the stimulus of any chemical signal) of cancerous versus noncancerous cells. They also analyzed the extracellular matrix molecules that were deposited by the two cell lines and found that cancerous cells deposited more hyaluronic acid (HA). The HA, in turn, affects motility, polarization and differentiation of cells.  Finally, the Hopkins team measured the level of expression of CD44, a cell surface receptor that recognizes HA, and found that metastatic cells express more CD44.

The next steps, Wirtz said, would be to validate these results using other metastatic cell lines.  To read the paper, which is published in an open access journal, follow this link: http://www.nature.com/srep/2013/130422/srep01449/full/srep01449.html

Excerpts from original press release by Princeton science writer Morgan Kelly were used.

 

 

 

 

INBT Seminar Aug. 22: New Questions in Aging

Everyone ages; it’s a fact. But as we age, must we also get sick? Scientists, engineers and clinicians are studying how cells change as we age. What they learn may help prevent the onset of disease.

Johns Hopkins Institute for NanoBioTechnology will host a half-day seminar “New Questions in Aging,” Aug. 22 from 10 a.m. until noon in the Hackerman Hall Auditorium (B-17).

Speakers include experts in the field of aging research.

Felipe Sierra

Felipe Sierra, PhD is director of the National Institute of Aging Division of Aging Biology at the National Institutes of Health. He will present the talk “Geroscience: Aging as the Major Risk Factor for Chronic Disease”  from 10-10:45 a.m.

Denis Wirtz, PhD, is the Theophilus H. Smoot Professor in the Chemical and Biomolecular Engineering at Johns Hopkins University and director of the Johns Hopkins Physical Sciences-Oncology Center. His talk is entitled “Single Cell Phenotyping for Studies in Aging;” 10:45 -11:00 a.m.

Denis Wirtz

Jeremy Walston, MD, is the Raymond and Anna Lublin Professor of Geriatric Medicine from the Johns Hopkins University School of Medicine, Division of Geriatric Medicine and Gerontology. His talk is entitled “A Biological Platform for Chronic Disease and Late Life Decline;” 11:00 to 11:15.

Questions and discussion on this interesting topic will follow the talks. This seminar is free and open to the entire Hopkins community. Faculty, students and staff are encouraged to attend for any or all portions of this seminar. For further information about the Johns Hopkins Physical Sciences-Oncology Center, go to http://psoc.inbt.jhu.edu/about/

Jeremy Walston

The Institute for NanoBioTechnology at Johns Hopkins University brings together 223 researchers from the Johns Hopkins Bloomberg School of Public Health, Krieger School of Arts and Sciences, School of Medicine, Applied Physics Laboratory, and Whiting School of Engineering to create new knowledge and new technologies at the interface of nanoscience and medicine.

 

Breast cancer highlighted at Homewood mini-symposium

A tumor cell breaking free and entering the blood stream. (From animation by Ella McCrea, Nathan Weiss and Martin Rietveld)

Breast cancer will be topic of at least two of the talks planned for a mini-symposium October 10 on the Homewood campus.

UPDATED: Click here for updated list of talk titles.

Students from Johns Hopkins Physical Sciences-Oncology Center (PSOC) and Center of Cancer Nanotechnology Excellence (CCNE) will hold their second mini-symposium of the year on October 10 at 9 a.m. in Hackerman Hall Auditorium. The symposia, scheduled each spring and fall on the Homewood campus, encourage an exchange of ideas between PhD students and postdoctoral fellows associated with these centers. The entire Hopkins community is invited to attend, and no RSVP is required.

Some of the talk titles include, from the department of Chemical and Biomolecular Engineering, “The Pulsing Motion of Breast Cancer Cell is Regulated by Surrounding Epithelial Cells” presented by Meng Horng Lee, a PSOC postdoctoral fellow in the Denis Wirtz lab; “Breast Tumor Extracellular Matrix Promotes Vasculogenesis” presented by Abigail Hielscher, a postdoctoral fellow in the Sharon Gerecht lab; and “Mucin 16 is a Functional Selectin Ligand on Pancreatic Cancer Cells” given by Jack Chen, a pre-doctoral fellow in the lab of Konstantinos Konstantopoulos. Additional speakers include postdoctoral fellow Pei-Hsun Wu, PhD, a from the Wirtz Lab and Koh Meng Aw Yong, a pre-doctoral student affiliated with Princeton University’s Physical Sciences-Oncology Center.

The purpose of these twice a year, student run mini-symposia is to facilitate communication among researchers working in laboratories studying the mechanistic aspects of cancer spread (i.e., those affiliated with the PSOC) and those working on novel means of using nanotechnology for cancer diagnosis or treatment (i.e., those associated with the CCNE). Anjil Giri coordinated the fall mini-symposium, a PSOC pre-doctoral fellow in the Wirtz lab , with Erbil Abaci, a PSOC pre-doctoral fellow with in the Gerecht lab. Visit the INBT website (inbt.jhu.edu) for further details, as additional speakers and talk titles will be announced.