Related Experiment Videos
A strategy to discover circulating angiogenesis inhibitors generated by human tumors
C Chen1, S Parangi, M J Tolentino
1Department of Surgery, Children's Hospital, Boston, Massachusetts 02115, USA.
Abstract:
The phenomenon of inhibition of tumor growth by tumor mass has been studied in many experimental animal systems and has been observed in several clinical scenarios. Not until the recent discovery of angiostatin, a circulating angiogenesis inhibitor generated in the presence of a murine Lewis lung tumor, has a satisfactory mechanism been proposed to explain this phenomenon. Thus far, no other animal or human tumors are known to generate angiostatin. In this study, we utilized a mouse corneal neovascularization model to detect circulating inhibitors of angiogenesis generated by three human tumors grown in immunodeficient mice: (a) the PC-3 human prostate carcinoma; (b) the CCL188 human colon carcinoma; and (c) the UBC urinary bladder carcinoma. Mice bearing these three primary tumors demonstrated significant inhibition of angiogenesis in the cornea induced by a pellet containing basic fibroblast growth factor. Corneas of mice bearing s.c. prostate and colon carcinomas showed significant inhibition of vessel length, clock-hours of neovascularization, and vessel density. However, corneas of mice bearing s.c. bladder carcinomas demonstrated significant inhibition of vessel density only. Three colon carcinomas (clone A, CX-1, and MIP101), the MDA-MB-435S breast carcinoma, the MM-AN melanoma, and the JE-3 choriocarcinoma did not significantly inhibit corneal neovascularization.
Insights
Tumors can inhibit their own growth by releasing circulating angiogenesis inhibitors. This study found that human prostate and colon tumors, but not bladder tumors, generate such inhibitors in a mouse model.
Area of Science:
- Oncology
- Vascular Biology
- Cancer Research
Background:
- Tumor growth inhibition by tumor mass is a known phenomenon.
- Angiostatin, a circulating angiogenesis inhibitor, was recently discovered associated with murine Lewis lung tumors.
- The mechanism for tumor self-inhibition was previously unclear, with no other known sources of angiostatin.
Purpose of the Study:
- To investigate whether human tumors generate circulating inhibitors of angiogenesis.
- To utilize a mouse corneal neovascularization model to detect these inhibitors.
- To assess the inhibitory potential of human prostate, colon, and bladder carcinomas.
Main Methods:
- A mouse corneal neovascularization model was employed.
- Human tumors (PC-3 prostate, CCL188 colon, UBC bladder) were grown in immunodeficient mice.
- Angiogenesis was induced by basic fibroblast growth factor pellets in the cornea.
- Inhibition was quantified by measuring vessel length, clock-hours of neovascularization, and vessel density.
Main Results:
- Mice bearing primary prostate and colon carcinomas showed significant inhibition of corneal angiogenesis (vessel length, clock-hours, density).
- Mice bearing primary bladder carcinomas showed significant inhibition of vessel density only.
- Several other human tumor cell lines (colon, breast, melanoma, choriocarcinoma) did not significantly inhibit corneal neovascularization.
Conclusions:
- Human prostate and colon carcinomas can generate circulating factors that inhibit angiogenesis.
- The UBC urinary bladder carcinoma demonstrated a weaker inhibitory effect.
- This suggests that some human tumors, like the murine Lewis lung tumor, can produce endogenous angiogenesis inhibitors.