Retroviral endostatin gene transfer inhibits growth of human lung cancer in a murine orthotopic xenotransplant model.
OBJECTIVE
The administration of endostatin, a potent anti-angiogenic agent, will be required for extended periods of time as a cancer treatment. The aim of the present study was to induce endogenous endostatin secretion in a continuous fashion, based on retroviral gene transfer. The tumor response was evaluated in an orthotopic murine tumor model of human lung cancer.


METHODS
Human non-small-cell lung cancer cells (KNS 62) were retrovirally transduced with the human endostatin gene. An orthotopic murine xenotransplant model was used to investigate tumor growth, metastases and survival. After 4 weeks of subcutaneous growth, endostatin expression was measured by immunoblot analysis in tumor lysates.


RESULTS
The growth of the subcutaneous tumors was significantly delayed, and orthotopic tumor growth and pleural metastases were significantly reduced in endostatin-transduced KNS 62 tumors. Prolongation of survival subsequent to orthotopic tumor induction was demonstrated. Strong endostatin expression was found in subcutaneous tumors after 4 weeks.


CONCLUSIONS
Retroviral transduction of the human endostatin gene is capable of achieving long-term endostatin expression. Endostatin transduction provides significant anti-tumor effects with regard to local tumor growth, metastases and survival.
Kurdow
Roland
R
Clinic for General and Thoracic Surgery, UKSH, Campus Kiel, Arnold-Heller Strasse 7, 24105, Kiel, Germany. rkurdow@surgery.uni-kiel.de
Boehle
Arnd S
AS
Ruhnke
Maren
M
Mendoza
Renata
R
Boenicke
Lars
L
Sipos
Bence
B
Schniewind
Bodo
B
Dohrmann
Peter
P
Kalthoff
Holger
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D043169:Endostatins / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D043169:Endostatins