Cancer in wildlife has recently received increasing attention as we appreciate the wide range of impacts of environmental change on both human and animal health, and that wild animals can serve as sentinels for human health. Every year approximately 200 live adult California sea lions (Zalophus californianus) strand along the west coast of the USA and are admitted to animal hospitals for care. Strikingly, almost 20% of adult animals that die in treatment have cancer: an aggressive, widely metastatic carcinoma of urogenital origin. The cause or causes of such a high prevalence of tumors in this population is unknown.
A gamma herpesvirus, OtarineHerpesvirus - 1 (OtHV-1), similar to human herpesvirus-8 associated with Kaposi's sarcoma in humans, has been identified and is present in a high proportion of the urogenital tissue examined to date. As such, an etiologic role for OtHV-1 has been postulated, although this virus is also present in healthy sea lion genital secretions.
In addition, sea lions accumulate high concentrations of organochlorines and other persistent organic pollutants, some of which are known to cause immune suppression, hormonal and metabolic disruption and genotoxicity in other species leading to cancer. These contaminants are widespread pollutants of the coastal environment, especially the Southern California Bight, where sea lions breed and forage. High levels of pollutants, especially PAHs occur in beluga whales of the St. Laurence estuary that also have high cancer rates. While the role of organochlorines in cancers of sea lions is still unknown, polychlorinated biphenyl (PCB) levels are higher in blubber of animals dying from cancer than in those dying from acute trauma, and significant levels of organochlorines cross the placenta exposing developing fetal tissues.
Genetics also likely play a role in the development of this cancer. Inbreeding in sea lions increases the susceptibility to neoplasia, as well as to infectious disease, and the MHC Class II Zaca-DRB.A locus is associated with the presence of cancer in these animals. Newly published research showed that carcinoma was significantly associated with homozygosity at a single microsatellite locus, Pv11. This maps to intron 9 of the heparanase 2 gene which is associated in humans with mulitple carcinomas.
Thus a number of factors are associated with the presence of cancer in California sea lions. Determining the relevant importance of each in cancer development, however, has been hindered by our limited access to wild animals for logistic, legal and ethical reasons, the confounding factors influencing contaminant burden and infection status, and our limited knowledge of the sea lion immune system. For example, contaminants are lipophilic and mobilized from blubber as animals lose weight. Thus as cancer cases lose weight due to illness, pollutants will be concentrated so cause or consequence of cancer cannot be distinguished.
Understanding the etiology and mechanisms involved in cancer development in sea lions is vital as these animals share both a food supply (salmon, hake, squid, rockfish, anchovies, sardines) as well as coastal waters with humans. The genome of the California sea lion has now being mapped by a team of undergraduates at San Diego State University lead by Elizabeth Dinsdale (http://sealiongenome.org). This advance offers a unique opportunity to investigate the origin of the cancer in the sea lion and to define the development of the malignant process.
This achievement, coupled with the establishment of an interdisciplinary team, the Sea Lion Cancer Consortium (SLiCC), will facilitate and advance our understanding of the biology of this complex common cancer occurring in sea lions in California waters.
Current Research Directions
- Case control study to determine relative contributions of contaminants, viral infection and genetics to risk of developing urogenital carcinoma.
- Characterizing the role of OtHV-1 in the pathogenesis of urogenital carcinoma of California sea lions.
- Utilizing proteomics to identify target pathways and therapeutic targets in sea lion urogenital carcinoma.