Expression of CD44 isoforms in human breast carcinoma xenografts is not influenced by the treatment of mice with cytostatics or (anti-)hormones

Anticancer Res. 1999 May-Jun;19(3A):1977-87.

Abstract

CD44 standard (s) and variant (v) isoforms have been discussed to be implicated in progression and metastasis of different malignomas. For breast carcinomas, the results of different studies are contradictory. These apparent discrepancies suggest that CD44 isoforms are not available on the tumour cell surface, but could be regulated by different endogenous and exogenous factors. Here we report the regulation of CD44 isoforms in xenografted breast cancer cell lines by cytostatics, hormones and antihormones. The human breast cancer models MDA-MB 435, MCF-7, NCI/ADR, 4296, 4151 and 4134 were transplanted into the mammary fat pad of nude mice. When tumours reached a palpable size, animals were treated with farmorubicine, cyclophosphamide, estradiol, tamoxifen or progesterone, respectively. At different times after treatment, serum and tumours were taken. The expression of CD44 and its isoforms was determined by immunohistochemistry and RT-PCR, serum levels were measured by human specific ELISA kits. Serum levels of CD44s and v6 varied among the tumours. For 3/6 tumours we found differences between control groups and treated animals. Immunohistochemical results remained unchanged: each tumour showed a specific pattern of CD44 expression, but this pattern did not change when the animals received cytostatics, hormones or antihormones. The same held true for RT-PCR-results. Also, the time of tumour collection had no influence on CD44 expression. Therefore, it can be concluded, that in the xenografted breast cancer cell lines a regulation of CD44 isoforms by farmorubicine, cyclophosphamide, estradiol, progesterone or tamoxifen could not be found, while serum levels were influenced in some cases probably due to tumour cell kill and shedding of surface proteins into blood stream.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cyclophosphamide / pharmacology
  • Epirubicin / pharmacology
  • Estradiol / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hyaluronan Receptors / biosynthesis*
  • Hyaluronan Receptors / genetics
  • Ki-67 Antigen / analysis
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Progesterone / pharmacology
  • Protein Isoforms / biosynthesis*
  • Protein Isoforms / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Tamoxifen / pharmacology
  • Transplantation, Heterologous
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / transplantation

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Hormonal
  • Hyaluronan Receptors
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • Epirubicin
  • Progesterone
  • Estradiol
  • Cyclophosphamide