Evan Keller, University of Michigan

Three Problems:

• Why is prostate cancer osteoblastic (i.e. most cancers when they spread to bone result in bone resorption (i.e., osteolytic); whereas, prostate cancer results in bone production (i.e. osteoblastic).
• Why does prostate cancer preferentially metastasize to bone as opposed to other sites.
• How can we successfully treat metastases that are highly heterogenous (i.e  within one patient, different metastases have different properties).

Background Papers:

• Histopathological Assessment of Prostate Cancer Bone Osteoblastic Metastases
• OSTEOBLASTS IN PROSTATE CANCER METASTASIS TO BONE

Robert Getzenberg, Johns Hopkins University

Three Questions:

• Metastatic cancer cells have amplified evolutionary capabilities that allow them to develop resistance to therapeutic approaches.  This may be enhanced by niches/microenvironments being emptied by “sensitive” populations that do not survive.  What role do physical and/or structural properties play in the development of resistance and how can modification of these by used to hinder the evolution of cancer?
• The concept that cancer cells metastasize as single cells may not be correct.  Groups of cancers cells along with what appear to be perhaps supporting players have been identified.  Do cells, other than the tumor cells themselves, “travel” with the cancer cell and aid in the development of metastatic sites?  If so, are they from the site of origin or are they recruited from other sources?  Can we image these?
• It appears that heat can be used to increase the sensitivity cancer cells to other forms of therapy and that the price that the cancer cells pays for being so able to develop resistance to therapy is a sensitivity to microenvironmental stresses.  What physical properties of the cells have been altered that creates this sensitivity to stresses?  

Don Coffey, Johns Hopkins University

Central Question:

Why is there so much variation (heterogeneity) within solid tumors in relation to  cell structure and function and how might this relate to energy, information transfer, and self-organization?

Gary Stein, University of Massachusetts

Three Problems:

• Epigenetic control in tumorigenesis, tumor progression and metastasis ¹
• Nuclear microenvironments in biological control and cancer ²
• Cell adhesion and motility in tumor progression ³

References:

¹Zaidi SK, Young DW, Montecino M, Lian JB, van Wijnen AJ, Stein JL, Stein GS. (2010) Mitotic bookmarking of genes: a novel dimension to epigenetic control. Nature Reviews Genetics Aug;11(8):583-9. Epub 2010 Jul 13.

²Zaidi SK, Young DW, Javed A, Pratap J, Montecino M, van Wijnen AJ, Lian JB, Stein JL, Stein GS   (2007) Nuclear microenvironments in biological control and cancer.  Nature Reviews Cancer, 7:454-463.

³Altieri DC, Languino LR, Lian JB, Stein JL, Leav I, van Wijnen AJ, Jiang Z, Stein GS. Article.  (2009) Prostate cancer regulatory networks. J Cell Biochem. Aug 1;107(5):845-52.

Lance Munn, Harvard

Three Questions:

• Can we identify patients who would benefit from treatment aimed at preventing metastasis or further metastasis? 
• How does the accumulation of compressive stress affect invasion and metastasis?
• What role do host stromal cells or cancer cell cooperation play in invasion and metastasis?

 

Background Papers:

• Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis
• Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed?
• Mechanisms of collective cell migration at a glance

Yibin Kang, Princeton

Questions

• Do tumor cells behave differently as solitary cells (disseminated tumor cells or micrometastasis) and as overt metastasis.  Is a critical mass required for tumor cells to manifest their full malignant potential and how does this relates to metastatic dormancy?
• Is there a fitness cost for tumor cells to overcome different hurdles of metastasis?  For example, when tumor cells undergo epithelial mesenchymal transition to invade and migrate, are they more susceptible to certain drugs. 
• What are the key molecular pathways that mediate tumor-stromal interactions in metastasis?  How to we effectively deliver therapeutics to disseminated tumor cells or micrometastasis to prevent distant recurrence?

Background Papers

• ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis
• A multigenic program mediating breast cancer metastasis to bone
• Imaging transforming growth factor-b signaling dynamics and therapeutic response in breast cancer bone metastasis

Ken Pienta, University of Michigan

Three questions:

• How efficient is the metastatic process? What are the qualities of a cancer cell that is a successful metastatic seed?
• How do the physical qualities of the target organ affect the establishment of a metastasis?
• How do cells survive the turbulence of the circulation?

Background Papers:

• The Lethal Phenotype of Cancer: The Molecular Basis of Death Due to Malignancy
• Pathogenesis and Treatment of Prostate Cancer Bone Metastases: Targeting the Lethal Phenotype

Meeting Logistics

Dates:
November 1-2, 2010 (October 31st, registration and opening discussion with refreshments in the evening for those available, time 6-8pm.)


Location:
Hilton-Arlington, 950 North Stafford Street, Arlington, VA 22203
Note: Reservations and hotel payment will be made via meeting coordinator.  Please forward your reservation dates to Sara. 

Directions & Transportation: Link

Travel:
Please make your own travel arrangements.  Attendee's are encouraged to make air/ground transportation reservations as early as possible to capitalize on reduced fares. Currently, the organizers are budgeted for air travel at the following RT rates: West coast ~$700; Mid-West, ~$600; and East Coast, ~$300. Air/ground transportation will be reimbursed after the meeting by UCSD. You will be given detailed instructions on how to submit your travel reimbursements at or shortly after the meeting.

Please be aware of the following restrictions: UC will reimburse you for economy/coach class air travel (or the equivalent of an economy/coach fare if you decide to fly business/first class) and original receipts are required. For those living within driving distance,  you may receive a mileage per diem (and parking fee reimbursement) if you use your personal vehicle. Taxis, shuttles and train expenses (within reasonable limits) will also be reimbursed.

Please forward your itinerary and ticket price to the meeting coordinator, Sara Bradley at sara.bradley@comcast.net.

Agenda:
Sunday, October 31st: registration and opening discussion with refreshments in the evening for those available, time 6-8pm.
Monday, November 1: talks and discussion will run the full day on Monday, dinner to follow.
Tuesday, November 2: talks and discussion will run to approximately 3pm.
Detailed agenda tba.


Meeting Coordinator:
Sara Bradley

Physics of Cancer Metastasis

Physics of Cancer Metastasis