Heterogeneity of cancer cells from a single human colon carcinoma

Dexter, Daniel L.; Spremulli, Ellen N.; Fligiel, Zuzana; Barbosa, James A.; Vogel, Renee; VanVoorhees, Abby; Calabresi, Paul

doi:10.1016/0002-9343(81)90312-0

Cited by 156 publications

(96 citation statements)

References 15 publications

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“…The human DLD-1 CRC cell line (Dexter et al, 1981) harbors one mutant K-ras G13D allele, and was obtained from the American Type Culture Collection. DLD-1 K-ras G13D was selectively disrupted by homologous recombination to generate the K-ras wt/null cell line Dks-8 (Shirasawa et al, 1993).…”

Section: Cell Linesmentioning

confidence: 99%

Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts

et al. 2008

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Section: Cell Linesmentioning

confidence: 99%

Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts

et al. 2008

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“…These lines are distinct in morphology, in chromosome number and in their responses to a number of chemical and physical cytotoxic agents (Leith et al, 1982a(Leith et al, ,b, 1984. In vivo, clone A cells produce poorly differentiated tumours, while D cells produce moderately differentiated colon cancers (Dexter et al, 1981). The A and D lines are maintained in tissue culture according to previously published procedures (Leith et al, 1982a(Leith et al, , b, 1984 and are replenished from frozen stock every 3-4 months.…”

Section: Tumour Linesmentioning

confidence: 99%

“…In this regard, we have been studying the biological characteristics of xenografted artificial heterogeneous tumours (AHTs). These are neoplasms comprised of admixtures of varying proportions of clonally related subpopulations (designated as A and D) originally derived from a human colon adenocarcinoma (Dexter et al, 1981). Zonality and compositional stability characteristics of unperturbed AHTs have been experimentally described (Leith et al, 1985(Leith et al, , 1987, and efforts to model AHT behaviour biomathematically have begun (Michelson et al, 1987a(Michelson et al, ,b,c, 1988Michelson, 1987 (1987).…”

mentioning

confidence: 99%

Competitive exclusion of clonal subpopulations in heterogeneous tumours after stromal injury

Leith

Michelson²,

As³

1989

Br J Cancer

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Summary Xenografted artificial heterogeneous tumours (AHTs) were created by admixing, in a ratio of 9:1 or 1:9, two clonal subpopulations (designated as clones A and D) obtained from a heterogeneous human colon adenocarcinoma. In unperturbed AHTs these percentages remain constant with increasing tumour size. At average volumes of 250 mm3, AHTs were X-irradiated (15 Gy) and changes in growth rate and composition assayed. A and D cells exhibited equivalent levels of survival after in vivo irradiation as determined by excision assay procedures. At about 2-3 weeks post-irradiation AHTs exhibited a significant enrichment of the majority population in both the 1:9 or 9:1 A:D AHTs. Additional studies were concomitantly performed to determine whether these changes were mostly a function of normal tissue damage or of parenchymal tumour cell killing. In these studies, the normal tissue only was irradiated, tumour cells were implanted one day after irradiation, and the composition of AHTs assayed as a function of time postirradiation. In these studies, similar shifts in composition with similar kinetics to that seen in the in situ irradiations were found. We therefore propose that these compositional shifts are mainly a reflection of radiation damage to the stromal microenvironment, which is consequently unable to support tumour growth adequately leading to competitive exclusion of the minority subpopulation.Many human solid cancers are clonally heterogeneous in composition . Mauro et al. (1986) and Hiddemann et al. (1986) have shown that approximately one-third of all human colorectal cancers contain two or more subpopulations based on flow cytometric analysis of DNA content. In this regard, we have been studying the biological characteristics of xenografted artificial heterogeneous tumours (AHTs). These are neoplasms comprised of admixtures of varying proportions of clonally related subpopulations (designated as A and D) originally derived from a human colon adenocarcinoma (Dexter et al., 1981). Zonality and compositional stability characteristics of unperturbed AHTs have been experimentally described (Leith et al., 1985(Leith et al., , 1987, and efforts to model AHT behaviour biomathematically have begun (Michelson et al., 1987a(Michelson et al., ,b,c, 1988Michelson, 1987 (1987).The tumour bed effect (TBE) is a well-documented phenomenon in which pre-irradiation of normal tissues modifies the subsequent growth behaviour of transplanted neoplasms in the damaged region (Hewitt & Blake, 1968;Urano & Suit, 1970;Jirtle et al., 1978;Trott & Kummemehr, 1983;Begg & Terry, 1983Ito et al., 1985;Milas et al., 1986). Due to the intimate relationship between tumour parenchyma and normal tissue stroma (Siemann et al., 1981), we thought that the relationship between TBE expression and tumour heterogeneity warranted investigation. While zonality and compositional stability aspects of unperturbed colon AHTs have been described (Leith et al., 1987), it is important to see if such characteristics would change in the face of a stress...

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“…The heterogeneity of human colorectal cancer has been well documented (Brattain et al, 1984). Studies on colorectal cell lines have illustrated that this heterogeneity is also observed in vitro (Brattain et al, 1984;Rosenthal et al, 1977;Drewinko et al, 1984;Dexter et al, 1981). The wide variation in antigen expression on dividing cells from the same tumour implies that this heterogeneity is also probably expressed at the stem cell level although caution must be exerted at extrapolating directly from dividing cells in vitro to stem cells in vivo.…”

Section: Cumentioning

confidence: 99%

Antigenicity of newly established colorectal carcinoma cell lines

Durrant¹,

Robins²,

Pimm³

et al. 1986

Br J Cancer

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Summary Cells from two adenocarcinomas, an adenoma and a metastatic node were isolated in soft agar. Expression of antigens, CEA, Y haptenic blood group and 791T-p72, defined by a range of candidate antibodies for tumour targeting was assessed.All of the cells expressed low levels of CEA but high levels of the Y haptenic blood group antigen although there was enormous inter and intraclonal variation. Of particular interest was the membrane expression of 791T-p72 antigen on all of the dividing tumour cells as previous studies had shown that 791T/36 antibody reacted with tumour stromal elements rather than malignant cell surfaces.The DNA content was abnormal in all of the cells whether they were derived from diploid or aneuploid primary tumours. They all grew readily in athymic mice and at least one monoclonal antibody, 791T/36, localised efficiently within these xenografts.Clonogenic cells therefore expressed the three tumour-associated antigens, several at higher levels than observed in the primary tumour. Monoclonal antibody 'cocktails' should therefore allow antibody mediated drug cytotoxicity to be effective at eradicating rapidly dividing tumour cells.

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Heterogeneity of cancer cells from a single human colon carcinoma

Cited by 156 publications

References 15 publications

Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts

Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts

Competitive exclusion of clonal subpopulations in heterogeneous tumours after stromal injury

Antigenicity of newly established colorectal carcinoma cell lines

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