Abstract

Tumor invasion/metastasis is still the major cause of death in cancer patients. Membrane type-1 matrix metalloproteinase (MT1-MMP) is directly related to tumor invasion/metastasis. To accurately and quickly distinguish the risk of invasion/metastasis of primary tumor cells, it is urgent to develop a simple and precise quantitative method to distinguish the expression level of MT1-MMP. In this work, we have constructed red fluorescent Au clusters with peroxidase-like properties that could specifically bind to MT1-MMP on human cervical cancer cells. After MT1-MMP was labelled with Au clusters, we could visually see red fluorescence of MT1-MMP on cervical cancer cells via fluorescence microscopy and catalytic color imaging using an ordinary optical microscope. The constructed Au clusters contained 26 Au atoms; thus, the amount of MT1-MMP on cervical cancer cells could be accurately quantified using inductively coupled plasma mass spectrometry (ICP-MS). More importantly, the invasion/metastasis capabilities of the cervical cancer Siha, Caski and Hela cells with different MT1-MMP amounts could be accurately distinguished by fluorescence/catalysis qualitative imaging and ICP-MS quantitative analysis. This method of qualitative/quantitative analysis of tumor-associated proteins on cancer cells has great potential for accurately diagnosing aggressive tumor cells and assessment of their invasion/metastasis risk.

Highlights

  • Despite the tremendous progress in understanding the occurrence of cancer, the 5-year survival rate of distant metastases tumors has not improved significantly compared to the localized tumor in most cancer patients, and invasion/metastasis is still the main cause of death in cancer patients [1,2,3,4]

  • Matrix metalloproteinases (MMPs) play a deterministic role in tumor cells invading the surrounding microenvironments of cleaving the extracellular matrix (ECM) [8,9,10], and matrix metalloproteinases (MMPs) are closely related to cancer cell growth, invasion, angiogenesis, and metastasis [11,12,13,14]

  • Our results suggested that the amount of cells was directly related to the invasion/metastasis abilities of cervical cancer cells

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Summary

Introduction

Despite the tremendous progress in understanding the occurrence of cancer, the 5-year survival rate of distant metastases tumors has not improved significantly compared to the localized tumor in most cancer patients, and invasion/metastasis is still the main cause of death in cancer patients [1,2,3,4]. Tumor cells must invade the extracellular matrix (ECM) of the primary tumor [5,6,7]. Matrix metalloproteinases (MMPs) play a deterministic role in tumor cells invading the surrounding microenvironments of cleaving the ECM [8,9,10], and MMPs are closely related to cancer cell growth, invasion, angiogenesis, and metastasis [11,12,13,14]. Among many kinds of MMPs, membrane type-1 matrix metalloproteinase (MT1-MMP) is extremely important, as it directly degrades several ECM molecules, such as collagen types I, II, III, laminins-1 and -5, fibrin, fibronectin, vitronectin, and aggrecan [15,16,17,18,19,20].

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