Human lung cancers growing on extracellular matrix: expression of oncogenes and growth factors.
The goal of this study was to evaluate the extracellular matrix (ECM) as a model for growing human lung cancers and to study the feasibility of its application for cellular and molecular studies of tumor biology. Bovine corneal endothelial cell ECM coated dishes were evaluated as a growth substrate for tumor cultures. Growth success, morphology and oncoprotein/growth factor expression for 74 different lung cancers (adenocarcinoma, epidermoid carcinoma and small cell carcinoma) were compared after seeding fresh surgical explants onto bovine corneal endothelial cell ECM and plastic culture substrate. Nineteen out of 74 tumors (26%) plated on ECM demonstrated measurable growth. Growth on ECM was superior to growth on plastic for the lung tumors. All 19 tumor cultures showed malignant morphology and functions. They were examined under the light microscope, and in all cases pre- and post-cytology confirmed malignancy. Tumor cells seeded on ECM retained their malignant phenotype in comparison to tumors grown on plastic. Several oncoproteins (c-myc, c-Ha-ras, c-erbB-2) and growth factors/receptors (EGF, EGF-R, TGF alpha) were immunostained. These analyses were performed immediately after disaggregation of tumor cells obtained surgically and after seeding on ECM or plastic. Strong expression of oncoproteins/growth factors was detected in tumor cells immediately after surgery or when the cells were plated on ECM. On the other hand, moderate or no expression was observed in the same type of cells on plastic.
Pavelic
K
K
Ruder Boskovic Institute, Laboratory of Molecular Oncology, Zegreb, Croatia.
Antonic
M
M
Pavelic
L
L
Pavelic
J
J
Pavelic
Z
Z
Spaventi
S
S
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002449:Cell Aggregation; D002455:Cell Division; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000096:biosynthesis; D066246:ErbB Receptors / Q000032:analysis* / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000502:physiology; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D011003:Ploidies; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha / Q000032:analysis* / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; C501009:HRAS protein, human