scholarly journals Foetal and cancer patient fibroblasts produce an autocrine migration-stimulating factor not made by normal adult cells

1988 ◽  
Vol 90 (3) ◽  
pp. 391-399 ◽  
Author(s):  
S.L. Schor ◽  
A.M. Schor ◽  
A.M. Grey ◽  
G. Rushton
Keyword(s):  
Cancer Patient ◽  
Cancer Patients ◽  
Three Dimensional ◽  
Conditioned Media ◽  
Normal Adult ◽  
Biochemical Basis ◽  
Migration Stimulating Factor ◽  
Stimulating Factor ◽  
Adult Fibroblasts ◽  
Adult Cells

We have previously reported that (1) the migration of foetal and adult fibroblasts into three-dimensional collagen matrices is differentially affected by cell density, and (2) skin fibroblasts from cancer patients commonly display a foetal-like mode of migratory behaviour. Data presented here indicate that differences in the migration of these cell types are particularly apparent in cultures plated at high density (i.e. at cell confluence); under these conditions, foetal fibroblasts and the foetal-like fibroblasts of cancer patients migrate into the three-dimensional collagen matrix to a significantly greater extent than do normal adult cells. In this initial study concerned with the biochemical basis of these observations, we report that medium conditioned by either foetal or cancer patient fibroblasts stimulates the migration of confluent adult cells. This stimulation of migration is specific to confluent cells, as the migration of subconfluent adult fibroblasts is unaffected by these conditioned media. Gel filtration chromatography of foetal fibroblast-conditioned medium indicates that migration-stimulating activity is recovered in a single peak with an apparent molecular mass in the range of 50–60 (X 10(3]. The active migration stimulating factor (MSF) in both foetal and cancer patient fibroblast-conditioned media appears to be a protein stable at acid pH, but inactivated by heat, alkaline pH and reductive alkylation. MSF produced by foetal and cancer patient fibroblasts is presumably responsible for the characteristically elevated levels of migration displayed by these cells in confluent culture, thereby suggesting an autocrine mode of action for this factor.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Fibroblasts from cancer patients display a mixture of both foetal and adult-like phenotypic characteristics

1988 ◽  
Vol 90 (3) ◽  
pp. 401-407 ◽  
Author(s):  
S.L. Schor ◽  
A.M. Schor ◽  
G. Rushton
Keyword(s):  
Breast Cancer ◽  
Cancer Patient ◽  
Cancer Patients ◽  
Normal Adult ◽  
Population Doubling ◽  
Collagen Gels ◽  
Phenotypic Characteristics ◽  
Biochemical Basis ◽  
Adult Cells

We have previously reported that foetal and adult fibroblasts display distinctive migratory phenotypes when cultured on three-dimensional collagen gels. Both skin and tumour-derived fibroblasts from a significant proportion of patients with breast cancer were subsequently observed to display foetal-like migratory behaviour. In the accompanying paper concerned with the biochemical basis of these observations, we presented evidence that foetal fibroblasts and the foetal-like fibroblasts of cancer patients produce a soluble migration-stimulating factor (MSF) not made by normal adult cells. Data are presented here indicating that: (1) the spontaneous foetal-to-adult transition in migratory phenotype that foetal fibroblasts undergo after approximately 50–55 population doublings in vitro is correlated with a cessation of MSF production; (2) breast cancer patient fibroblasts do not undergo such a phenotypic transition and continue to produce MSF for their entire in vitro lifespan. These foetal-like cancer patient fibroblasts do, however, resemble normal adult cells by a number of other criteria, including population doubling potential, enhanced migration in the presence of serum compared to platelet-poor plasma, saturation cell density and morphology in confluent culture. These data indicate that the fibroblasts of breast cancer patients express a mixture of both foetal and adult phenotypic characteristics. Such a finding is consistent with published information indicating that foetal-to-adult transitions in various fibroblast phenotypic characteristics occur in a temporally disparate fashion during normal development, and further imply that cancer patient fibroblasts have undergone only certain of these transitions.

scholarly journals Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
JungHo Kong ◽  
Heetak Lee ◽  
Donghyo Kim ◽  
Seong Kyu Han ◽  
Doyeon Ha ◽  
...  
Keyword(s):  
Machine Learning ◽  
Cancer Patient ◽  
Cancer Patients ◽  
Three Dimensional ◽  
Predictive Biomarkers ◽  
Drug Efficacy ◽  
Cancer Drug ◽  
Drug Responses ◽  
Anti Cancer ◽  
Culture Models

Abstract Cancer patient classification using predictive biomarkers for anti-cancer drug responses is essential for improving therapeutic outcomes. However, current machine-learning-based predictions of drug response often fail to identify robust translational biomarkers from preclinical models. Here, we present a machine-learning framework to identify robust drug biomarkers by taking advantage of network-based analyses using pharmacogenomic data derived from three-dimensional organoid culture models. The biomarkers identified by our approach accurately predict the drug responses of 114 colorectal cancer patients treated with 5-fluorouracil and 77 bladder cancer patients treated with cisplatin. We further confirm our biomarkers using external transcriptomic datasets of drug-sensitive and -resistant isogenic cancer cell lines. Finally, concordance analysis between the transcriptomic biomarkers and independent somatic mutation-based biomarkers further validate our method. This work presents a method to predict cancer patient drug responses using pharmacogenomic data derived from organoid models by combining the application of gene modules and network-based approaches.

scholarly journals Differences between adult and foetal fibroblasts in the regulation of hyaluronate synthesis: correlation with migratory activity

1989 ◽  
Vol 94 (3) ◽  
pp. 577-584
Author(s):  
W.Y. Chen ◽  
M.E. Grant ◽  
A.M. Schor ◽  
S.L. Schor
Keyword(s):  
Cell Density ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Close Correlation ◽  
Cell Types ◽  
Size Class ◽  
Major Constituent ◽  
Migratory Activity ◽  
Adult Fibroblasts ◽  
Adult Cells

We have previously reported that confluent foetal fibroblasts migrate into three-dimensional collagen gel matrices to a significantly greater extent than do adult cells. Hyaluronic acid (HA) is a major constituent of the extracellular matrix deposited by fibroblasts and has been demonstrated to stimulate the migration of a number of different cell types. Previous studies have indicated that the synthesis of HA by normal adult skin fibroblasts declines significantly when the cells achieve confluence. Data presented in this paper indicate that foetal fibroblasts differ from adult cells in this respect, in that they do not show an inverse relationship between cell density and HA synthesis, i.e. confluent foetal fibroblasts continue to produce approximately the same amount of HA as do subconfluent cells. These data suggest that the synthesis of relatively high levels of HA by foetal fibroblasts at confluence may be causally related to the elevated migration displayed by these cells. In this context, a close correlation was observed between the level of HA synthesized by confluent foetal and adult fibroblasts and the differential migratory activity displayed by these cells. Such differences in HA synthesis and migratory behaviour were only apparent at cell confluence, with subconfluent foetal and adult fibroblasts being indistinguishable in terms of these two criteria. Our data further reveal that: (1) cell density affects the size class of HA synthesized by both foetal and adult cells; and that (2) there is a considerable degree of heterogeneity amongst the nine different fibroblast lines examined in this study in terms of the size class of HA that they produce.

PSYCHOLOGICAL REHABILITATION AND SCREENING OF EMOTIONAL STRESS IN CANCER PATIENTS

2017 ◽  
Vol 63 (2) ◽  
pp. 316-319 ◽  
Author(s):  
Valentina Chulkova ◽  
Tatyana Semiglazova ◽  
Margarita Vagaytseva ◽  
Andrey Karitskiy ◽  
Yevgeniy Demin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Cancer Patient ◽  
Cancer Patients ◽  
Emotional Stress ◽  
Self Esteem ◽  
Breast Cancer Patients ◽  
Psychological Study ◽  
Psychological Assistance

Psychological rehabilitation is an integral part of rehabilitation of a cancer patient. Psychological rehabilitation is aimed at a patient adaptation in the situation of the disease and improvement his quality of life. Understanding of an oncological disease is extreme and (or) crisis situation and monitoring dynamics of the psychological statement of a patient allows using differentiated approach in the provision of professional psychological assistance. The modified scale of self-esteem level of distress (IPOS) was used for screening of mental and emotional stress of cancer patients. There were selected groups of cancer patients who were most in need of professional psychological assistance. Results of a psychological study of one of these groups - breast cancer patients - are presented.

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