Cell heterogeneity and subpopulations in solid tumors characterized by simultaneous immunophenotyping and DNA content analysis

Abstract

Background Heterogeneity in human malignant tumors is a well‐described phenomenon and of interest with regard to subpopulations with differences in clonality, metastatic potential, and response to therapy under different treatment regimes. The aim of this study was the simultaneous characterization of surface markers and DNA content of solid tumors to identify tumor cell subpopulations and to study the association between the expression of antigens and DNA content. Methods In the present study, six different malignant tumors grown as xenografts in nude mice were characterized by five‐parameter flow cytometry. Immunophenotyping was performed using a variety of direct fluorescence‐conjugated antibodies. In all cases, simultaneous detection of DNA content was done after staining with 7‐aminoactinomycin D. Results Tumor cells were characterized by light scatter properties, antigen expression, and DNA content. Tumor cell heterogeneity, subpopulations, and DNA content‐dependent antigen expression were identified. Conclusions This method offers the possibility of characterizing solid tumors according to their immunophenotype and DNA content. The results obtained can be used to identify changes in immunophenotypic and DNA profiles of tumor cell populations before and after therapy and might be useful to define parameters predictive for response to therapy. Cytometry 41:172–177, 2000 © 2000 Wiley‐Liss, Inc.

Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis

“…Further divergence of the clone may result in subpopulations of neoplastic cells, some of which gain the capacity to metastasize. [13][14][15][16][17] Although genetic heterogeneity is the norm in melanoma, [18][19][20][21][22] it would be expected that a primary melanoma and its metastases would share at least one or more genetic alterations. Studies to date have shown that loss of heterozygosity (LOH) on 9p and 10q has been associated with early-stage primary disease, whereas LOH on 6q, 1p, 8q, and 11q has been associated with progression and metastasis.…”

Genetically Heterogeneous and Clonally Unrelated Metastases May Arise in Patients With Cutaneous Melanoma

“…Genetic divergence after clonal expansion may lead to the development of several subpopulations of neoplastic cells with only rare cells gaining the capacity to metastasize. 11,12,15,23,29 Examinations of subpopulations of tumor cells within a number of malignancies have shown that many types of tumors exhibit tremendous genetic heterogeneity. Whether metastases derive from a single clone which populates the majority of the primary tumor or whether metastases arise from a small, minority of cells with a divergent genetic makeup and with the capability of metastasis is uncertain.…”

Photo-oxidative action in MCF-7 cancer cells induced by hydrophobic cyanines loaded in biodegradable microemulsion-templated nanocapsules

“…However, as reported by Yordanov et al, a small decrease in the delivery efficiency of the loaded polymeric nanocapsules may be a consequence of partial erosion of PBCA nanocapsules (42). Additionally, some differences in uptake may be related to a discrepancy in divisional state of the cells or be caused by cell heterogeneity of the used tumor cell lines (43,44). Further studies are needed to clarify this problem.…”