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A New In Vitro Assay for Human Tumor Angiogenesis: Three-Dimensional Human Tumor Angiogenesis Assay

From the John Wayne Cancer Institute (SAG), Santa Monica, California; Department of Surgery (EAW), Louisiana State University Health Sciences Center, New Orleans, Louisiana; The Veterans Affairs Medical Center (EAW), New Orleans, Louisiana; and The Louisiana State University, Health Sciences Center, Stanley S. Scott Cancer Center (EAW), New Orleans, Louisiana.

Correspondence: Address correspondence and reprint requests to: Eugene A. Woltering, MD, FACS, Louisiana State University Health Sciences Center, Department of Surgery, 1542 Tulane Avenue, New Orleans, LA 70112; Fax: 504-563-4633; E-mail: ewolte{at}lsuhsc.edu

Background: A human tissue–based angiogenesis assay is needed to study the biology of angiogenesis in human tumor tissue and to tailor drug selection for patients.

Methods: Fragments of tumor tissue are embedded in fibrin gels containing medium 199, endothelial growth medium, fetal bovine serum, and -aminocaproic acid. Tumor implants sprout angiogenic vessels that progressively grow into the fibrin matrix. The differential growth pattern of tumor cells and angiogenic vessels in the fibrin gel matrix separates the angiogenic vessels and the tumor stroma into independently observable regions (vessel and tumor compartments). The reproducibility of the assay was tested by using fresh tissue obtained from human tumor xenografts (IMR-32 [neuroblastoma], MDA-MB-231 [breast cancer], and LNCaP [prostate cancer]) grown in nude mice and from fresh surgical breast and thyroid cancer specimens.

Results: All tumor fragments studied showed angiogenic sprouting into the fibrin matrix. This created an angiogenic vessel compartment, which was separate from the tumor fragment. The capillary nature of sprouting was confirmed histologically by factor VIII immunohistochemistry. The angiogenic growth fraction was >80% in all groups studied.

Conclusions: This assay may allow functional assessment of the angiogenic potential of human tumors and simultaneous evaluation of a therapeutic agent’s antitumor and antiangiogenic effects by virtue of its dual-compartmental structure.

Key Words: In vitro • Human • Tumor • Angiogenesis • Assay