Overview
A link between hemostasis and cancer is well recognized. Numerous clinical studies have shown that the expression of procoagulants (e.g., tissue factor) by tumor cells correlates strongly with a poor prognosis and metastatic disease for multiple cancers. More recently it has become clear that these associations are not merely epiphenomena. Rather, hemostatic factors actively contribute to tumor progression and dissemination. The primary interest of our laboratory is understanding how hemostatic system components support cancer progression and dissemination. Our laboratory has shown that a major aspect of the role of hemostasis in cancer biology involves interactions with the innate immune system.
Hemostatic Factors and Metastasis
| Metastasis |
 |
Hemostatic factors support metastasis. The genetic
alteration/elimination of key hemostatic system components
dramatically diminishes pulmonary metastases (B) relative
to control mice (A). |
| Colitis |
 |
Fibrinogen supports inflammatory colitis. Genetically
altering the interaction of fibrinogen with the inflammatory
cell receptor, aMb2, significantly diminishes colitis. |
Metastatic disease is the primary cause of most cancer treatment failures and cancer-related deaths. We have shown that a crucial factor in the metastatic process is the ability of metastatic tumor cells to initiate thrombin generation and subsequent platelet/fibrin deposition. The precise mechanisms coupling thrombin to tumor cell metastasis are only beginning to be fully understood. One particularly intriguing hypothesis supported by substantial data from our laboratory is that local platelet/fibrin deposits surrounding a newly formed micrometastasis provides protection from innate immune surveillance mechanisms, such as natural killer (NK) cells. Our goal is to understand how metastatic tumor cells hijack the function of the hemostatic system and how hemostatic factors prevent the clearance of metastasis by NK cells. This knowledge holds the promise of novel therapies for treating or preventing metastatic disease.
Hemostasis and Colitis-Associated Cancer
Chronic inflammation is a significant antecedent risk factor in the development of multiple cancers. A prime example of this is the strong association between long-standing inflammatory bowel disease (i.e., ulcerative colitis and Crohn’s disease) and colon cancer. However, the factors that drive the pathological activation of inflammation in this setting remain poorly defined. Our laboratory has shown that hemostatic factors, particularly fibrinogen and platelets, are key regulators of the inflammatory response in colitis and support the progression of colitis-associated colon cancer. A major focus of our laboratory is understanding how hemostatic factors, which have traditionally been thought of as distinct from innate immunity, actually regulate the inflammatory response in colitis and support colitis-associated cancer. In addition to furthering our knowledge of the regulation of inflammation and the pathophysiology of colitis, it is our goal to use this knowledge to develop new paradigms for the treatment and/or prevention of inflammation-induced cancers.
Contact Us
You can contact Dr. Palumbo's Lab by calling 513-636-8617 (Emily Kimball, Joe's secretary), by faxing 513-636-3549 (Hem/Onc), or by emailing Dr. Palumbo at joe.palumbo@cchmc.org.
