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Breast cancer integrin expression and its relationship to tumour invasion and metastasis

Hock, Gerald Gui Peng; (1996) Breast cancer integrin expression and its relationship to tumour invasion and metastasis. Masters thesis (M.Surg), UCL (University College London). Green open access

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Abstract

The integrins are receptors consisting of varying a and subunits that modulate cell adhesion to the extracellular matrix. Loss of cell-matrix interaction in malignant disease might result in less adhesive cells predisposed to metastasis. Integrin expression and function in primary breast cancer was therefore investigated in relation to nodal status. Integrin subunits were measured using immunohistochemistry on cryostat sections of primary breast cancer from lymph node negative (LN-) and lymph node positive (LN+) women. Loss of the [alpha]1[beta]l, [alpha]2[beta]l, [alpha]3[beta]l, [alpha]6[beta]l, [alpha]v[beta]l and [alpha]v[beta]5 integrins were significantly related to positive nodal status at the time of clinical presentation. The accuracy of a clinical score to predict nodal status using the [beta]1, [alpha]v and [alpha]1 subunits in conjunction with tumour size, vascular invasion and multifocal disease was 89.1[percent]. The consequence of altered integrin expression on cell-matrix adhesion was evaluated in-vitro. Primary tumours from LN- and LN+ women were isolated using immunomagnetic separation and added to triplicate wells coated with either fibronectin, vitronectin, laminin or collagen. Primary breast cancer cells from LN+ patients failed to adhere to their matrix compared to LN- patients. Receptor specificity was demonstrated by inhibition of cell-matrix adhesion using integrin antibodies and peptide inhibitors. The influence of the integrins on chemoinvasion was assessed using breast cancer cell lines plated on 8 [mu]m porous filters coated with matrix protein ligands. The MDA-MB-231 and Hs578T cell lines displayed significant chemoinvasion that was inhibited by preventing cell-matrix adhesion with integrin antibodies. Altered integrin expression in primary breast cancer is related to nodal status and has been shown to be functionally related to tumour cell adhesion. Integrin expression may thus be of prognostic significance and could allow patient selection for axillary surgery. Perturbation of integrin function in malignant cell lines reduced invasiveness and may be a potential therapeutic target.

Type: Thesis (Masters)
Qualification: M.Surg
Title: Breast cancer integrin expression and its relationship to tumour invasion and metastasis
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10104272
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