Lactate-induced inhibition of tumor cell proliferation

Marx, E; Mueller-Klieser, W.; Vaupel, Peter

doi:10.1016/0360-3016(88)90017-x

Cited by 33 publications

(14 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Growth pattern and clonogenicity of MCF-7 and HT-29 cells in monolayer cul ture are known from the literature [19][20][21][22], The doubling times of both cell lines calcu lated in this study are comparable to those documented in previous investigations. The effects of TNF-a on MCF-7 cells have also been studied by other investigators [3][4][5], In the present report, a cytokine dose of ap proximately 200 IU rhTNF-a/ml for 30 min caused a significant cytotoxicity in MCF-7 cells.…”

Section: Discussionsupporting

confidence: 77%

Influences of Recombinant Human Tumor Necrosis Factor-α on Growth and Oxygen Consumption of MCF-7 and HT-29 Cells

Kunz¹,

Mueller‐Klieser²

1991

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

The effect of recombinant human tumor necrosis factor-α (rhTNF-α) on cellular growth and oxygen consumption was investigated using human mammary carcinoma MCF-7 and human colon adenocarcinoma HT-29 cells. Cellular growth was quantified by monolayer growth curves. The respiratory activity of the cells was assessed by a photometric technique. A single dose of rhTNF-α of 200 IU/ml for 30 min induced a significant growth retardation in MCF-7 cells when given 1 or 5 days after plating. No effect of rhTNF-α on HT-29 monolayer growth was observed at this dose. A growth retardation similar to that obtained in MCF-7 cells was achieved by a 10-fold rise in the rhTNF-α concentration in medium with HT-29 cells. Application of rhTNF-α was associated with an increase in the cellular oxygen consumption Q by factors of 2 and 4 in MCF-7 and HT-29 cells, respectively. Whereas oxygen uptake increased continuously in MCF-7 cells throughout the entire period of plateau-phase growth, only a transient increase in O₂ consumption rate was observed in HT-29 with values almost returning to the control level in the early plateau phase. Thus, differences in the sensitivity to the growth-inhibitory activity of rhTNF-α between MCF-7 and HT-29 cells are correlated with differences in the kinetics of changes in cellular respiration after application of rhTNF-α, possibly reflecting different capacities for damage repair. The changes in oxygen uptake upon rhTNF-α seem to be genetically fixed, since they persist in several cell generations descending from the treated cells both for MCF-7 and HT-29.

show abstract

Section: Discussionsupporting

confidence: 77%

Influences of Recombinant Human Tumor Necrosis Factor-α on Growth and Oxygen Consumption of MCF-7 and HT-29 Cells

Kunz¹,

Mueller‐Klieser²

1991

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…The growth retardation was not enhanced any further in 20 mM vs. 9 m~ lactate, suggesting a saturation of this effect in spheroids. This is different from the reaction of EMT6 monolayer cells to corresponding lactate concentrations where such a saturation was not observed (Marx et al, 1988).…”

Section: Discussionmentioning

confidence: 90%

“…, 1971). Growth-inhibiting effects of lactate within corresponding concentration ranges have been identified in previous investigations on monolayer cultures of various cell lines (Marx et al, 1988).…”

mentioning

confidence: 91%

Biological response of multicellular emt6 spheroids to exogenous lactate

Bourrat-Floeck

Groebe

Mueller‐Klieser

1991

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

The influence of elevated lactate concentrations, as found in tumor microregions, on cellular growth, viability, and metabolic state was studied employing the multicellular spheroid model. Spheroids of EMT6/Ro cells were cultured at 37 degrees C in 5% or 20% (v/v) oxygen, using stirred media with various concentrations of exogenous lactate ranging from 0.0 mM (standard conditions) to 20.0 mM. Elevated concentrations of exogenous lactate led to a considerable decrease of the maximum spheroid diameter at growth saturation, e.g., for 20% O2 from around 1700 microns to 700 microns in 0.0 and 20.0 mM lactate respectively. Histological investigations showed that the thickness of the viable cell rim was increased by elevated lactate concentrations in 20% O2, whereas this correlation was reversed in 5% O2. Cultivation of spheroids in increasing lactate concentrations was associated with a shift of metabolic pathways from net production to increased utilization of lactate in both 20% and 5% O2, as determined by standard enzymatic assays. Oxygen tension (PO2) values measured with micro-electrodes were less in spheroids cultured in high lactate (9.0 and 20.0 mM) than under standard conditions, irrespective of the external oxygen concentration. This finding reflected a substantial increase in the cellular O2 consumption with elevated external lactate levels. At given lactate concentrations, respiration rates that were derived from measured PO2 distributions by theoretical considerations were significantly lower in 5% O2 than in 20% O2.

show abstract

“…The data obtained from cell cultures indicated that lactate levels in the extracellular compartment should be elevated to around 10 mmol/ L for 1 h to obtain a substantial growth retardation (Marx et al 1988). Previous studies have demonstrated that animals tolerated glucose concentrations in the blood of as high as 40 mmol/r, although thermosensitization was already achieved at much lower concentrations, e.g., at twice the physiological level of 5 mmol/L (Calderwood and Dickson 1980).…”

Section: Introductionmentioning

confidence: 93%

“…The growth-inhibitory effect of exogenous lactate on tumour cells has been demonstrated in both conventional monolayer cultures (Marx et al 1988) and multicellular spheroids (Bourrat-FIoeck et al 1991). Two major mechanisms appeared to be involved in this effect: (i) a feedback inhibition of metabolism by its metabolic product; and (ii) interference with the regulation of intracellular pH.…”

Section: Introductionmentioning

confidence: 97%

Tumour-growth inhibition by induced hyperglycaemia/hyperlactacidaemia and localized hyperthermia

Mueller-Klieser

Walenta

Kelleher

et al. 1996

International Journal of Hyperthermia

Self Cite

View full text Add to dashboard Cite

The present study was undertaken to exploit pathophysiological properties of solid tumours for a tumour-specific therapy. Experiments were carried out on DS-sarcomas implanted s.c. in the hind foot dorsum of Sprague Dawley rats. Treatment strategies included tumour acidification, lactate accumulation and disturbance of the microcirculation by induced systemic hyperglycaemia/hyperlact-acidaemia (15-25/10 mmol/L; for 60 min) as well as localized hyperthermia (water-bath; 43 degrees C, 30 min.). A special infusion solution was developed for the systemic treatment containing glucose, lactic acid and organic buffer without inorganic ions. Growth kinetics of tumour volume and animal survival were taken as endpoints in order to quantify therapeutic efficiency. After a single treatment with combined modalities, i.e., with hyperglycaemia/hyperlactacidaemia and hyperthermia, approximately 50% of the tumours showed complete remission in three independent series of experiments; around 40% of the animals survived more than two months. In the untreated control group, all animals died from the disease within 10-15 days after tumour implantation. The overall effect on tumour volume changes of the combined therapy was supra-additive compared to that of treatment with hyperthermia or hyperglycaemia/hyperlactacidaemia alone. However, treated animals either showed a dramatic response to the combination of treatments with complete tumour remission or hardly responded at all, justifying a subdivision into responders and non-responders. Pathophysiological mechanisms responsible for this behaviour have to be elucidated in future studies. Nevertheless, the present study represents an approach to an efficient tumour therapy with a potential application in clinical oncology in the not too distant future.

show abstract

Lactate-induced inhibition of tumor cell proliferation

Cited by 33 publications

References 8 publications

Influences of Recombinant Human Tumor Necrosis Factor-α on Growth and Oxygen Consumption of MCF-7 and HT-29 Cells

Influences of Recombinant Human Tumor Necrosis Factor-α on Growth and Oxygen Consumption of MCF-7 and HT-29 Cells

Biological response of multicellular emt6 spheroids to exogenous lactate

Tumour-growth inhibition by induced hyperglycaemia/hyperlactacidaemia and localized hyperthermia

Contact Info

Product

Resources

About

Lactate-induced inhibition of tumor cell proliferation

Cited by 33 publications

References 8 publications

Influences of Recombinant Human Tumor Necrosis Factor-&alpha; on Growth and Oxygen Consumption of MCF-7 and HT-29 Cells

Influences of Recombinant Human Tumor Necrosis Factor-&alpha; on Growth and Oxygen Consumption of MCF-7 and HT-29 Cells

Biological response of multicellular emt6 spheroids to exogenous lactate

Tumour-growth inhibition by induced hyperglycaemia/hyperlactacidaemia and localized hyperthermia

Contact Info

Product

Resources

About

Influences of Recombinant Human Tumor Necrosis Factor-α on Growth and Oxygen Consumption of MCF-7 and HT-29 Cells

Influences of Recombinant Human Tumor Necrosis Factor-α on Growth and Oxygen Consumption of MCF-7 and HT-29 Cells