Research Program: Carcinogenesis & Chemoprevention
Professor, Department of Laboratory Medicine and Pathology

watte002@umn.edu
612-626-9113 — office
612-626-9193, 612-626-9197 - lab
Preferred method of contact: e-mail or office phone

Research Interests

Chemoprevention and carcinogenesis

This laboratory has been interested in chemoprevention of carcinogenesis primarily in animal models. Ongoing studies are directed at identifying chemopreventive agents that would be effective in preventing the occurrence of carcinogen induced cancer of the lung. Considerable emphasis has been placed on the use of aerosol technology since this brings the chemopreventive agent into direct contact with the target tissue. Two categories of chemopreventive agents are being investigated. The first are synthetic compounds and the second are dietary constituents, some crude and other in pure form. More recently we have been interested in the implications of the existence of a possible new component in the carcinogenic process termed an "Interlocker." A critical event in the sequence of events occurring during carcinogenesis is the development of irreversibility. The term "Interlocker" is used to denote the process by which irreversibility is brought about. Two examples are being explored. The first is built around the occurrence of several common features found in cancers of solid organs. These include a loss of control of cell proliferation, disorganization and infiltration. The concept is that the Interlocker is like a collar which binds together these common features irreversibly into a whole entity. It becomes fully active at the transition of precancer to cancer. One possibility is that this Interlocker involves aberrant glycoproteins. A second concept of an Interlocker is quite different. Central to this concept is the recognition that a critical feature of cancer is disorganization. An important manifestation of disorganization is loss of cell/cell adhesions. A striking finding in this regard is the loss of E-cadherin cell/cell adhesions. Its loss has been shown to occur in carcinogenesis in a large number of tissues. The existence of an Interlocker would be important. For cancer prevention it could provide a target for intervention, and one existing until a late point in the progression of precancer to cancer. For a collar type of Interlocker an agent that would break the collar could convert the lesion from being irreversible to being reversible, at least early in cancer. Finally the conceptualization of the existence of Interlockers itself is of value in providing new areas of research and new ways of evaluating data.

Selected Publications

Estensen RD, Anderson WR, Galbraith AR, Hartle DE, Jordan MM, Ondrey FG, Wattenberg LW. A method of producing carcinoma in upper aerodigestive tree and esophagus of the Syrian golden hamster using wounding and instillation of N-methylnitrosourea. Cancer Epidemiol Biomarkers Prev. 2007;16:1644-1650.

Lam S, McWilliams A, LeRiche J, MacAulay C, Wattenberg L, Szabo E. A phase I study of Myo-inositol for lung cancer chemoprevention. Cancer Epidemiol Biomarkers Prev 2006;15:1526-31.

Wattenberg LW. An Interlocker concept of carcinogenesis. Cancer Epidemiol Biomarkers Prev. 2006;15:1425-1426.

Wattenberg LW, Wiedmann TS, Estensen RD. Chemoprevention of cancer of the upper respiratory tract of the syrian golden hamster by aerosol administration of difluoromethylornithine and 5-fluorouracil. Cancer Res. 2004;64:2347-2349.

Wattenberg LW, Wiedmann TS, Estensen RD, Zimmerman CL, Galbraith AR, Steele VE, Kelloff GJ. Chemoprevention of pulmonary carcinogenesis by brief exposures to aerosolized budesonide or beclomethasone dipropionate and by the combination of aerosolized budesonide and dietary myo-inositol. Carcinogenesis 2000;21:179-182.