Phenotype modulation of tumor cell growth outlined by cell morphological patterns.

MAA Castro, MSc a, b, F Klamt, MSc a, c, G Schwartsmann, MD, PhD c, I Grivicich, MSc c, JCF Moreira, PhD a.

a Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. b Lutheran University of Brazil, Canoas, RS, Brazil. c SOAD, Comprehensive Cancer Center, Lutheran University of Brazil, Canoas, RS, Brazil.

AIM: We previously described that polarity of tumor cells are closely related to intercellular-contact degree (Cancer Lett, 145:65-72, 1999). In the current study, we present a model for cell growth as a function of cell phenotype (which include cell shape) using six human cell lines (A549, NCI-H596 and NCI-H520 lung carcinomas; HT29 and SW620 colon carcinomas; and U251 glioma cell line). METHODS: Monolayer cells in exponential growth at various densities were incubated at 37oC in a 5% CO2 humidified atmosphere and were quantified every 24-hours period during seven days by sulforhodamine B staining assay to produce cell growth curves. For each cell line we obtained three empirical growth parameters (initial cell density, cell growth rate and carry capacity - the maximal cell density) and two cell shape parameters (cell polarity (f) and cell deformation index (i) - a morphological relationship among spreading and confluent cell polarity). Cellular morphology measures were obtained by phase contrast photomicrographs analyses in the NIH-image program. RESULTS: We have found that cell polarity (f) and cell deformation index (i) are directly proportional to growth rate and carry capacity, respectively. The (f) and (i) parameters have shown to follow the growth curves data of cells organized in monolayer (A549, NCI-H596, U251 and SW620 cell lines) and multilayer (NCI-H520 and HT29; cell lines that promptly form cellular foci). A growth function was obtained accordingly to (f) and (i) parameters and compared with established empirical growth models (i.e. Gompertz and Logistic). CONCLUSION: Our study supports the idea that cell growth kinetic can be modulated by phenotype organization of cells attached on a substrate inside the cultured area.

KEY WORDS: Cell shape, morphological organization, growth kinetic, mathematical modeling, human carcinoma cell lines.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prognostic Markers.