Tumor Budding, Micropapillary Pattern, and Polyploidy Giant Cancer Cells in Colorectal Cancer: Current Status and Future Prospects.

Shiwu Zhang,Dan Zhang,Xipeng Zhang,Zhengduo Yang

doi:10.1155/2016/4810734

Abstract

We previously reported that polyploid giant cancer cells (PGCGs) induced by CoCl2 could form through endoreduplication or cell fusion. A single PGCC formed tumors in immunodeficient mice. PGCCs are also the key contributors to the cellular atypia and associate with the malignant grade of tumors. PGCCs have the properties of cancer stem cells and produce daughter cells via asymmetric cell division. Compared with diploid cancer cells, these daughter cells express less epithelial markers and acquire mesenchymal phenotype with importance in cancer development and progression. Tumor budding is generally recognized to correlate with a high recurrence rate, lymph node metastasis, chemoresistance, and poor prognosis of colorectal cancers (CRCs) and is a good indicator to predict the metastasis and aggressiveness in CRCs. Micropapillary pattern is a special morphologic pattern and also associates with tumor metastasis and poor prognosis. There are similar morphologic features and molecular phenotypes among tumor budding, micropapillary carcinoma pattern, and PGCCs with their budding daughter cells and all of them show strong ability of tumor invasion and migration. In this review, we discuss the cancer stem cell properties of PGCCs, the molecular mechanisms of their regulation, and the relationships with tumor budding and micropapillary pattern in CRCs.

Highlights

Colorectal cancer (CRC) is one of the most common malignant tumors and its incidence ranks the third of malignant tumors [1]
Increasing evidences confirmed the important role of polyploid giant cancer cells (PGCCs) and tumor budding in predicting the metastasis and patient’s prognosis of CRCs [7, 8]
We recently reported that PGCCs can be purified from human ovarian and breast cancer cells lines and primary human ovarian tumors with the use of chemical hypoxic mimetic, cobalt chloride (CoCl2) [12, 15, 21, 36,37,38], and confirmed that these cells were formed through cell fusion and produced daughter cells via asymmetric cell division

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignant tumors and its incidence ranks the third of malignant tumors [1]. Increasing evidences confirmed the important role of polyploid giant cancer cells (PGCCs) and tumor budding in predicting the metastasis and patient’s prognosis of CRCs [7, 8]. The daughter cells budded from PGCCs expressed EMT-related proteins and show strong ability of tumor invasion and migration. Tumor budding is similar to the morphological features of micropapillary pattern [16,17,18,19,20]. Based on the morphologic features, protein expression, and biologic behaviors, we speculate that these daughter cells budded from PGCCs fall into the broad term of tumor budding and micropapillary cancer pattern [12, 15, 21].

PGCCs and Cancer Stem Cells

Tumor Budding and Its Clinical and Pathologic Significances

The Role of EMT in the Process of Tumor Budding and PGCCs with Daughter Cells

Findings

Future Prospects of Tumor Budding and Single Stromal PGCCs