Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Abstract

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer

“…Therefore, a transfer route of POPs via LDL-receptor mediated endocytosis is possible. Notably, tumor cells have an increased need for structural elements and are thereby known to up-regulate LDL receptors (Pires et al 2012). These mechanisms may result in increased LDL-POP transport into the tumor cells.…”

Uso de carmustina associada a nanoemulsões ricas em colesterol (LDE) para tratamento da aterosclerose induzida em coelhos

“…As partículas de LDL são removidas da circulação pela captação de receptores de membrana especializados que internalizam essas partículas para o interior das células, como LDL-r (Pires et al, 2012) e LRP-1 (Boucher & Philippe, 2011).…”

“…Esses receptores reconhecem a apoproteína B (apoB-100), presente na LDL, e a apoproteína E (apoE), presente nos quilomícrons remanescentes, VLDL, IDL e HDL (Wilson et al, 1998;Jeon & Blacklow, 2005;Pires et al, 2012). Os receptores de LDL são agrupados em depressões na membrana celular e revestidas por clatrina.…”

“…(Brown & Goldstein, 1986;Vitols et al, 1990;Jeon & Blacklow, 2005;Beglova & Blacklow, 2005;Pires et al, 2012;Schekman, 2013). As células neoplásicas, as quais proliferam-se rapidamente, precisam de grande quantidade de colesterol para a síntese de novas membranas.…”

“…O LRP-1 é um receptor endocítico pertencente à família do receptor de LDL (Emonard et al, 2014) e é abundantemente expresso em tecidos do fígado, cérebro, placenta (Pires et al, 2012;Emonard et al, 2014) e parede vascular associado principalmente a macrófagos e células de músculo liso (Llorent-Cortés & Badimon, 2005).…”