Preoperative administration of erythropoietin stimulates tumor recurrence after surgical excision of colon cancer in mice by a vascular endothelial growth factor-independent mechanism.
BACKGROUND
It has been suggested that preoperative administration of erythropoietin (Epo) in patients with gastrointestinal cancer reduces transfusional needs and is also associated with lower morbidity. On the other hand, experimental and clinical studies show that Epo might enhance tumor growth and angiogenesis. Our aim was to ascertain whether preoperative administration of Epo has any effect on tumor recurrence after curative surgery using an experimental model of colon cancer.


METHODS
We induced tumors by injecting B51LiM colon cancer cells into the cecal wall of Balb/c mice. We randomized the animals into three groups of treatment with (1) recombinant human Epo, (2) recombinant mouse Epo, or (3) vehicle alone, for 12 d until cecectomy. On postoperative day 12, we killed mice and analyzed tumor recurrence. We measured serum levels of vascular endothelial growth factor and determined vascular endothelial growth factor expression and tumor microvessel density by immunohistochemistry. We also investigated the in vitro effect of Epo on B51LiM cell line proliferation.


RESULTS
All three groups displayed tumor recurrence, but the final tumor load score and total tumoral weight were higher in the two groups that included Epo. The differences were statistically significant when we compared the recombinant mouse Epo group with the control group. We found no evidence of increased angiogenesis or enhanced cell proliferation as possible mechanisms of Epo-induced recurrence.


CONCLUSIONS
Preoperative administration of Epo stimulates tumor recurrence in an animal model of colon cancer. Our results point to the need for further research on the mechanisms of tumor growth enhancement by Epo, to better understand the benefits or disadvantages of Epo treatment.
Colorectal Surgery Unit, Department of Surgery, Hospital del Mar, Barcelona, Spain.
Marta
M
Pascual
Bernhard
B
Bohle
Sandra
S
Alonso
Xavier
X
Mayol
Silvia
S
Salvans
Luis
L
Grande
Miguel
M
Pera
D000230:Adenocarcinoma / Q000601:surgery*; D000740:Anemia / Q000188:drug therapy; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000601:surgery*; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced*; D009389:Neovascularization, Pathologic; D011300:Preoperative Care / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D004921:Erythropoietin