Cancer cell dormancy: mechanisms and implications of cancer recurrence and metastasis

Abstract

More recently, disease metastasis and relapse in many cancer patients several years (even some decades) after surgical remission are regarded as tumor dormancy. However, the knowledge of this phenomenon is cripplingly limited. Substantial quantities of reviews have summarized three main potential models that can be put forth to explain such process, including angiogenic dormancy, immunologic dormancy, and cellular dormancy. In this review, newly uncovered mechanisms governing cancer cell dormancy are discussed, with an emphasis on the cross talk between dormant cancer cells and their microenvironments. In addition, potential mechanisms of reactivation of these dormant cells in certain anatomic sites including lymph nodes and bone marrow are discussed. Molecular mechanism of cellular dormancy in head and neck cancer is also involved.

<p>High Tiam1 expression predicts positive lymphatic metastasis and worse survival in patients with malignant solid tumors: a systematic review and meta-analysis</p>

“…First, metastasis is an essential hall marker of cancer and always leads to poor survival. [41][42][43] Numerous studies suggested that Tiam1 contributed to invasion and metastasis in various cancers, including osteosarcoma, 44 retinoblastoma, 45 gastric cancer, 46 CRC, [47][48][49][50][51] hepatocellular carcinoma, 25,52 breast cancer, 53 cholangiocarcinoma, 54 cervical cancer, 20 ovarian cancer, 55 nasopharyngeal cancer, 8,16 laryngeal cancer, 56 thyroid carcinoma, 57 nom-small cell lung cancer, 48 pancreatic cancer 6,58,59 and oral squamous cell carcinoma 27 Malliri et al reported that Tiam1 could facilitate E-cadherin-based adhesions between cancer cells in mouse intestinal tumors and human colon tumors, resulting in invasion and metastasis 60 Epithelial-mesenchymal transition (EMT) is a key process of enhancing cancer cell migration, invasion and metastasis. [28][29][30][31] Liu et al reported that Tiam1 overexpression could promote invasiveness and metastasis of thyroid carcinoma in vitro and in vivo by activating Wnt/EMT pathway 57 Similarly, Ding 6 and Yang et al 20 that Tiam1 overexpression could also boost invasion and metastasis of pancreatic cancer and cervical cancer by inducing EMT.…”

Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer

“…Also, the paradox role of pro-and anti-proliferative action of the immune system is shown in tumor evolution [22]. Also, inherent difficulties in detecting and characterizing micrometastatic lesions/individual cells in the patient is another hurdle to assess the relative contribution of various mechanisms of dormancy in the clinical setting [23]. However, the new emerging methodologies, namely microfluidics based on analyzing microliters of serum samples may enable detection of single cells, as wells as DTCs and may aid to capture dormancy dynamics at a single-cell resolution (reviewed in [24][25][26][27]).…”

Lymph node resection induces the activation of tumor cells in the lungs

“…Papers published recently have supported the theory that lymph node vessels provide exit routes for metastatic tumor cells to the systemic circulation . From another point of view, it has been shown in clinical studies that tumor cells attached to lung blood vessels are not activated for a considerable period of time, but these dormant tumor cells can be activated by surgical intervention, such as lymph node dissection . In preliminary studies, we have created a mouse model in which dormant tumor cells in lung metastatic lesions are activated after lymph node dissection .…”

“…13,14 From another point of view, it has been shown in clinical studies that tumor cells attached to lung blood vessels are not activated for a considerable period of time, but these dormant tumor cells can be activated by surgical intervention, such as lymph node dissection. 15,16 In preliminary studies, we have created a mouse model in which dormant tumor cells in lung metastatic lesions are activated after lymph node dissection. [10][11][12] In this model, the lung metastases were activated after excision of the lymph node into which the tumor cells had been inoculated.…”