Malignant Breast Epithelium Selects for Insulin-like Growth Factor II Expression in Breast Stroma

Evidence for Paracrine function

Christian Singer, Audrey Rasmussen, Helene S. Smith, Marc E. Lippman, Henry T. Lynch, Kevin J. Cullen

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Paracrine interactions between stromal and epithelial cells are important influences on the growth and malignant behavior of breast cancers. Insulin-like growth factors I and II (IGF-I and II) are expressed by fibroblasts in benign and malignant breast lesions, and both are strong mitogens for a number of breast cancer epithelial cell lines in vitro. We have analyzed the stromal mRNA expression of IGF-I and IGF-II in matched sets of fibroblast cell lines derived from three locations in the affected breast of eight patients with breast cancer: (a) the breast tumor itself; (b) surrounding normal breast tissue; and (c) overlying breast skin. IGF-I expression was easily detected in all fibroblasts derived from normal breast tissue. In general, lesser amounts of IGF-I mRNA were detected in fibroblasts derived from breast tumors or skin. In contrast, IGF-II expression was detected at very low levels in only 3 of 8 normal breast fibroblasts, but was present in 6 of 8 tumor fibroblasts. IGF-II mRNA was expressed in all skin fibroblasts tested. IGF-n-negative stromal fibroblasts from normal breast, which were plated at low density and allowed to grow to confluence in the presence of MCF-7 breast tumor epithelial cells, demonstrated a marked increase in IGF-II mRNA expression. IGF-II in situ hybridization studies confirmed that IGF-II expression is seen at high levels in stroma of many invasive breast cancers but not normal breast We conclude that paracrine influences, mediated by soluble factors released by breast tumor epithelium, are able to specifically increase expression of IGF-II in breast stroma, most likely by a process of clonal selection.

Original languageEnglish
Pages (from-to)2448-2454
Number of pages7
JournalCancer Research
Volume55
Issue number11
StatePublished - Jun 1 1995

Fingerprint

Insulin-Like Growth Factor II
Breast
Epithelium
Breast Neoplasms
Fibroblasts
Insulin-Like Growth Factor I
Messenger RNA
Epithelial Cells
Skin
Cell Line
Stromal Cells
Mitogens
In Situ Hybridization

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Malignant Breast Epithelium Selects for Insulin-like Growth Factor II Expression in Breast Stroma : Evidence for Paracrine function. / Singer, Christian; Rasmussen, Audrey; Smith, Helene S.; Lippman, Marc E.; Lynch, Henry T.; Cullen, Kevin J.

In: Cancer Research, Vol. 55, No. 11, 01.06.1995, p. 2448-2454.

Research output: Contribution to journalArticle

Singer, C, Rasmussen, A, Smith, HS, Lippman, ME, Lynch, HT & Cullen, KJ 1995, 'Malignant Breast Epithelium Selects for Insulin-like Growth Factor II Expression in Breast Stroma: Evidence for Paracrine function', Cancer Research, vol. 55, no. 11, pp. 2448-2454.
Singer, Christian ; Rasmussen, Audrey ; Smith, Helene S. ; Lippman, Marc E. ; Lynch, Henry T. ; Cullen, Kevin J. / Malignant Breast Epithelium Selects for Insulin-like Growth Factor II Expression in Breast Stroma : Evidence for Paracrine function. In: Cancer Research. 1995 ; Vol. 55, No. 11. pp. 2448-2454.
@article{5327475d0d924d078e055438fd0a7f9c,
title = "Malignant Breast Epithelium Selects for Insulin-like Growth Factor II Expression in Breast Stroma: Evidence for Paracrine function",
abstract = "Paracrine interactions between stromal and epithelial cells are important influences on the growth and malignant behavior of breast cancers. Insulin-like growth factors I and II (IGF-I and II) are expressed by fibroblasts in benign and malignant breast lesions, and both are strong mitogens for a number of breast cancer epithelial cell lines in vitro. We have analyzed the stromal mRNA expression of IGF-I and IGF-II in matched sets of fibroblast cell lines derived from three locations in the affected breast of eight patients with breast cancer: (a) the breast tumor itself; (b) surrounding normal breast tissue; and (c) overlying breast skin. IGF-I expression was easily detected in all fibroblasts derived from normal breast tissue. In general, lesser amounts of IGF-I mRNA were detected in fibroblasts derived from breast tumors or skin. In contrast, IGF-II expression was detected at very low levels in only 3 of 8 normal breast fibroblasts, but was present in 6 of 8 tumor fibroblasts. IGF-II mRNA was expressed in all skin fibroblasts tested. IGF-n-negative stromal fibroblasts from normal breast, which were plated at low density and allowed to grow to confluence in the presence of MCF-7 breast tumor epithelial cells, demonstrated a marked increase in IGF-II mRNA expression. IGF-II in situ hybridization studies confirmed that IGF-II expression is seen at high levels in stroma of many invasive breast cancers but not normal breast We conclude that paracrine influences, mediated by soluble factors released by breast tumor epithelium, are able to specifically increase expression of IGF-II in breast stroma, most likely by a process of clonal selection.",
author = "Christian Singer and Audrey Rasmussen and Smith, {Helene S.} and Lippman, {Marc E.} and Lynch, {Henry T.} and Cullen, {Kevin J.}",
year = "1995",
month = "6",
day = "1",
language = "English",
volume = "55",
pages = "2448--2454",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Malignant Breast Epithelium Selects for Insulin-like Growth Factor II Expression in Breast Stroma

T2 - Evidence for Paracrine function

AU - Singer, Christian

AU - Rasmussen, Audrey

AU - Smith, Helene S.

AU - Lippman, Marc E.

AU - Lynch, Henry T.

AU - Cullen, Kevin J.

PY - 1995/6/1

Y1 - 1995/6/1

N2 - Paracrine interactions between stromal and epithelial cells are important influences on the growth and malignant behavior of breast cancers. Insulin-like growth factors I and II (IGF-I and II) are expressed by fibroblasts in benign and malignant breast lesions, and both are strong mitogens for a number of breast cancer epithelial cell lines in vitro. We have analyzed the stromal mRNA expression of IGF-I and IGF-II in matched sets of fibroblast cell lines derived from three locations in the affected breast of eight patients with breast cancer: (a) the breast tumor itself; (b) surrounding normal breast tissue; and (c) overlying breast skin. IGF-I expression was easily detected in all fibroblasts derived from normal breast tissue. In general, lesser amounts of IGF-I mRNA were detected in fibroblasts derived from breast tumors or skin. In contrast, IGF-II expression was detected at very low levels in only 3 of 8 normal breast fibroblasts, but was present in 6 of 8 tumor fibroblasts. IGF-II mRNA was expressed in all skin fibroblasts tested. IGF-n-negative stromal fibroblasts from normal breast, which were plated at low density and allowed to grow to confluence in the presence of MCF-7 breast tumor epithelial cells, demonstrated a marked increase in IGF-II mRNA expression. IGF-II in situ hybridization studies confirmed that IGF-II expression is seen at high levels in stroma of many invasive breast cancers but not normal breast We conclude that paracrine influences, mediated by soluble factors released by breast tumor epithelium, are able to specifically increase expression of IGF-II in breast stroma, most likely by a process of clonal selection.

AB - Paracrine interactions between stromal and epithelial cells are important influences on the growth and malignant behavior of breast cancers. Insulin-like growth factors I and II (IGF-I and II) are expressed by fibroblasts in benign and malignant breast lesions, and both are strong mitogens for a number of breast cancer epithelial cell lines in vitro. We have analyzed the stromal mRNA expression of IGF-I and IGF-II in matched sets of fibroblast cell lines derived from three locations in the affected breast of eight patients with breast cancer: (a) the breast tumor itself; (b) surrounding normal breast tissue; and (c) overlying breast skin. IGF-I expression was easily detected in all fibroblasts derived from normal breast tissue. In general, lesser amounts of IGF-I mRNA were detected in fibroblasts derived from breast tumors or skin. In contrast, IGF-II expression was detected at very low levels in only 3 of 8 normal breast fibroblasts, but was present in 6 of 8 tumor fibroblasts. IGF-II mRNA was expressed in all skin fibroblasts tested. IGF-n-negative stromal fibroblasts from normal breast, which were plated at low density and allowed to grow to confluence in the presence of MCF-7 breast tumor epithelial cells, demonstrated a marked increase in IGF-II mRNA expression. IGF-II in situ hybridization studies confirmed that IGF-II expression is seen at high levels in stroma of many invasive breast cancers but not normal breast We conclude that paracrine influences, mediated by soluble factors released by breast tumor epithelium, are able to specifically increase expression of IGF-II in breast stroma, most likely by a process of clonal selection.

UR - http://www.scopus.com/inward/record.url?scp=0029053398&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029053398&partnerID=8YFLogxK

M3 - Article

VL - 55

SP - 2448

EP - 2454

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 11

ER -