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dc.contributor.authorSchor, Ana M
dc.contributor.authorRushton, Graham
dc.contributor.authorFerguson, Janice E
dc.contributor.authorHowell, Anthony
dc.contributor.authorRedford, J
dc.contributor.authorSchor, Seth L
dc.date.accessioned2010-04-22T15:47:32Z
dc.date.available2010-04-22T15:47:32Z
dc.date.issued1994-10-01
dc.identifier.citationPhenotypic heterogeneity in breast fibroblasts: functional anomaly in fibroblasts from histologically normal tissue adjacent to carcinoma. 1994, 59 (1):25-32 Int. J. Canceren
dc.identifier.issn0020-7136
dc.identifier.pmid7927899
dc.identifier.doi10.1002/ijc.2910590107
dc.identifier.urihttp://hdl.handle.net/10541/97177
dc.description.abstractHistologically normal breast tissue was obtained from women undergoing surgery for benign breast lesions (n = 12) and mammary carcinomas (n = 15). Four fibroblast subpopulations (FI, FII, FIII and FIV) were isolated from these specimens by differential digestion and centrifugation. FI cells were the first to be released from the tissue digest and consequently assumed to be derived from the interlobular stroma; FIV fibroblasts were tightly associated with the epithelial organoids and are therefore believed to be of intralobular origin. These cells were characterised in terms of their migratory phenotype (classified as either foetal- or adult-like) and the production of motility factors according to previously described techniques. FI fibroblasts obtained from patients with benign breast lesions displayed a foetal migratory phenotype (10/11) and secreted detectable quantities of motility factors (11/11). In contrast, none of the FIV fibroblasts (0/10) obtained from these same patients displayed a foetal-like migratory phenotype or secreted motility factors. In the case of fibroblasts obtained from cancer patients, both FI (13/13) and FIV (13/13) fibroblasts displayed a foetal-like migratory phenotype and secreted motility factors. Fibroblasts were also derived from skin (n = 12) and breast fat tissue (n = 4) of certain patients. In agreement with our previously published observations, skin fibroblasts obtained from non-cancer and cancer patients also differed in terms of their migratory behaviour: none of the skin fibroblast lines (0/5) obtained from non-cancer patients were foetal-like, compared to 3/7 lines from cancer patients. All fat-derived fibroblasts (1 non-cancer and 3 cancer patients) were also foetal-like. Our results indicate (i) functional heterogeneity between FI and FIV fibroblasts of normal breast, and (ii) the presence of functionally aberrant (i.e., foetal-like) FIV fibroblasts in histologically normal breast tissue adjacent to a carcinoma.
dc.language.isoenen
dc.subjectBreast Canceren
dc.subject.meshAdipose Tissue
dc.subject.meshAdolescent
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshBreast
dc.subject.meshBreast Neoplasms
dc.subject.meshCell Count
dc.subject.meshCell Division
dc.subject.meshCell Movement
dc.subject.meshFemale
dc.subject.meshFibroblasts
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshPhenotype
dc.subject.meshSkin
dc.titlePhenotypic heterogeneity in breast fibroblasts: functional anomaly in fibroblasts from histologically normal tissue adjacent to carcinoma.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology, Christie Hospital NHS Trust, UK.en
dc.identifier.journalInternational Journal of Canceren
html.description.abstractHistologically normal breast tissue was obtained from women undergoing surgery for benign breast lesions (n = 12) and mammary carcinomas (n = 15). Four fibroblast subpopulations (FI, FII, FIII and FIV) were isolated from these specimens by differential digestion and centrifugation. FI cells were the first to be released from the tissue digest and consequently assumed to be derived from the interlobular stroma; FIV fibroblasts were tightly associated with the epithelial organoids and are therefore believed to be of intralobular origin. These cells were characterised in terms of their migratory phenotype (classified as either foetal- or adult-like) and the production of motility factors according to previously described techniques. FI fibroblasts obtained from patients with benign breast lesions displayed a foetal migratory phenotype (10/11) and secreted detectable quantities of motility factors (11/11). In contrast, none of the FIV fibroblasts (0/10) obtained from these same patients displayed a foetal-like migratory phenotype or secreted motility factors. In the case of fibroblasts obtained from cancer patients, both FI (13/13) and FIV (13/13) fibroblasts displayed a foetal-like migratory phenotype and secreted motility factors. Fibroblasts were also derived from skin (n = 12) and breast fat tissue (n = 4) of certain patients. In agreement with our previously published observations, skin fibroblasts obtained from non-cancer and cancer patients also differed in terms of their migratory behaviour: none of the skin fibroblast lines (0/5) obtained from non-cancer patients were foetal-like, compared to 3/7 lines from cancer patients. All fat-derived fibroblasts (1 non-cancer and 3 cancer patients) were also foetal-like. Our results indicate (i) functional heterogeneity between FI and FIV fibroblasts of normal breast, and (ii) the presence of functionally aberrant (i.e., foetal-like) FIV fibroblasts in histologically normal breast tissue adjacent to a carcinoma.


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