EXPRESSION OF CD44 STANDARD AND ISOFORMS IN HUMAN BREAST-CANCER XENOGRAFTS AND SHEDDING OF SOLUBLE FORMS INTO SERUM OF NUDE-MICE

Standard CD44 (CD44s) and variant isoforms (CD44v) are expressed on di fferent malignant cells and tissues. Their upregulation has been impli cated, in the progression and; metastasis of malignomas. In this work we addressed the question of whether these molecules are also expresse d on xenografted human breast carcinomas and if certain expression pat terns are correlated with biological parameters like tumour size, horm one receptor status, histology, growth rate, chemoresistance and micro environment. Additionally, we were interested in the shedding of solub le CD44 (sCD44) into the blood circulation of tumour bearing nude mice . The human breast carcinomas MCF-7, MCF-7/ADR, 4296 and MDA-MB435, 41 34 and 4151 were transplanted subcutaneously (sc) or into the mammary fat pad (mfp.) of nude mice. The expression of the CD44s, -v6, and -v9 isoforms was determined at different time points on tissue samples by immunohistochemistry or RT-PCR employing human-specific antibodies or primers, respectively. The serum concentration of CD44s and -v6 was m easured by human specific ELISAs. All tumours expressed CD44s. The low est level was observed in the MCF-7 cancer. The CD44v6 and -v9 sequenc es and epitopes were distinctly expressed in MCF-7/ADR, MDA-MB435, 413 4, 4151 and 4296, while MCF-7 lacked these isoforms. The highest serum concentration of the v6 isoform was detected in mice bearing the tumo ur 4296 with a high tendency for lymphogenic metastasis. The serum lev els of sCD44 were in 516 xenografts linearly correlated with the tumou r size. Interestingly, there was a remarkable difference between the t wo sublines MCF-7 and MCF-7/ADR: Both the tissue and serum levels of C D44 isoforms indicated that the development of multidrug resistance is accompanied by an alteration in the expression of membrane proteins d iscussed to be involved in metastasis. There was no relation of tissue expression with the transplantation site and the hormone receptor sta tus of the tumour lines. CD44s and its valiant isoforms are expressed in human xenotransplanted breast cancers in very different levels and patterns. The highest expression in the tumour 4296 is related to lymp hogenic metastasis while the absence of isoforms in the model MCF-7 is related to non-metastatic behaviour. CD44 is shed into the serum and can be used for monitoring of tumour growth.