Abstract
The evolution of squamous epithelial neoplasms induced by 7,12-dimethylbenz[a]anthracene (DMBA) in Syrian hamster buccal pouch epithelium (HBPE) and the angiogenic potential of a subpopulation of presumptive preneoplastic keratinocytes was evaluated by examining the ability of whole cell dissociates of HBPE and subpopulations of keratinocytes, or their 72-h serum-free conditioned media (CM), to induce neovascularization in rat corneas and directional migration of bovine adrenal gland capillary endothelial cells (BCE) in culture. Buccal pouches were treated in vivo twice weekly for 5 weeks with either DMBA, paraffin oil (PO) or received no treatment. Hamsters were killed at various times after the last application of carcinogen and single-cell suspensions were prepared by enzymatic dissociation. Angiogenesis was assayed by injecting HBPE cells, or by implanting Hydron pellets containing CM in corneas and observing directional ingrowth of capillary blood vessels. Directional migration of BCE under agarose was tested with CM. Angiogenic activity of DMBA initiated HBPE dissociates was detected initially at 4 and 5 weeks after treatment, was markedly depressed between weeks 8 and 16 and re-emerged in squamous papillomas at week 25. The pattern of expression of angiogenic activity was observed to parallel the frequency of development of a morphologically unique population of keratinocytes that was detected exclusively in cultures of DMBA-exposed HBPE. These unique cells, designated type II keratinocytes, potently stimulated neovascularization in vivo and directional migration of BCE in culture. These results demonstrate that angiogenie activity is an early manifestation of hamster pouch carcinogenesis and suggests that type II keratinocytes, presumptive preneoplastic cells in this model, are the principal source of this activity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 117-122 |
| Number of pages | 6 |
| Journal | Carcinogenesis |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1988 |
Funding
We are most grateful to Drs Gerald Shklar and Debajit Biswas of the Harvard School of Dental Medicine, Boston, MA for providing the HCPC-1 cell line and Dr Jitka Olander, Monsanto Corporation, St Louis, MO for the capillary endothelial cells. The technical assistance of Mrs Doreen Borkowski and Deborah Chappel are gratefully acknowledged. We thank Maryann Culbertson for careful typing of the manuscript. This work was supported by Grants RR-05370 and CA34160 from the National Institutes of Health and Human Services.
ASJC Scopus subject areas
- Cancer Research
